Search

Your search keyword '"Conforti, Fl"' showing total 28 results
Start Over Author "Conforti, Fl" Topic mutation
28 results on '"Conforti, Fl"'

1. Individual Oligogenic Background in p.D91A- SOD1 Amyotrophic Lateral Sclerosis Patients.

Author

Gentile G, Perrone B, Morello G, Simone IL, Andò S, Cavallaro S, and Conforti FL

Subjects
Adult, Aged, Alleles, Cohort Studies, Female, Heterozygote, Humans, Male, Middle Aged, Phenotype, Amyotrophic Lateral Sclerosis genetics, Mutation genetics, Superoxide Dismutase-1 genetics
Abstract

The p.D91A is one of the most common ALS-causing SOD1 mutations and is known to be either recessive or dominant. The homozygous phenotype is characterized by prolonged survival and slow progression of disease, whereas the affected heterozygous phenotypes can vary. To date, no genetic protective factors located close to SOD1 have been associated with the mild progressive homozygous phenotype. Using Next Generation Sequencing (NGS), we characterized a small cohort of sporadic and familial p.D91A- SOD1 heterozygous ( n = 2) or homozygous ( n = 5) ALS patients, to reveal any additional contributing variant in 39 ALS-related genes. We detected unique sets of non-synonymous variants, four of which were of uncertain significance and several in untranslated regions of ALS-related genes. Our results supported an individual oligogenic background underlying both sporadic and familial p.D91A cases irrespective of their p.D91A mutant alleles. We suggest that a comprehensive genomic view of p.D91A- SOD1 ALS patients may be useful in identifying emerging variants and improving disease diagnosis as well as guiding precision medicine.

Published
2021
Full Text
View/download PDF

2. Common mutations of interest in the diagnosis of amyotrophic lateral sclerosis: how common are common mutations in ALS genes?

Author

Perrone B and Conforti FL

Subjects
Amyotrophic Lateral Sclerosis diagnosis, Amyotrophic Lateral Sclerosis ethnology, C9orf72 Protein genetics, DNA Mutational Analysis methods, DNA Repeat Expansion, DNA-Binding Proteins genetics, Ethnicity genetics, Gene Frequency, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Molecular Diagnostic Techniques, Mutation, Missense, Protein Aggregation, Pathological genetics, RNA-Binding Protein FUS genetics, Sequence Analysis, DNA methods, Superoxide Dismutase-1 genetics, Amyotrophic Lateral Sclerosis genetics, Mutation
Abstract

Introduction: Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease predominantly affecting upper and lower motor neurons. Diagnosis of this devastating pathology is very difficult because the high degree of clinical heterogeneity with which it occurs and until now, no truly effective treatment exists., Areas Covered: Molecular diagnosis may be a valuable tool for dissecting out ALS complex heterogeneity and for identifying new molecular mechanisms underlying the characteristic selective degeneration and death of motor neurons. To date, pathogenic variants in ALS genes are known to be present in up to 70% of familial and 10% of apparently sporadic ALS cases and can be associated with risks for ALS only or risks for other neurodegenerative diseases. This paper shows the procedure currently used in diagnostic laboratories to investigate most frequent mutations in ALS and evaluating the utility of involved molecular techniques as potential tools to discriminate 'common mutations' in ALS patients., Expert Opinion: Genetic testing may allow for establishing an accurate pathological diagnosis and a more precise stratification of patient groups in future drug trials.

Published
2020
Full Text
View/download PDF

3. ALS and CHARGE syndrome: a clinical and genetic study.

Author

Ungaro C, Citrigno L, Trojsi F, Sprovieri T, Gentile G, Muglia M, Monsurrò MR, Tedeschi G, Cavallaro S, and Conforti FL

Subjects
Adult, C9orf72 Protein genetics, DNA Helicases genetics, DNA-Binding Proteins genetics, Female, High-Throughput Nucleotide Sequencing, Humans, Kinesins genetics, Amyotrophic Lateral Sclerosis genetics, CHARGE Syndrome genetics, Genetic Predisposition to Disease, Mutation
Abstract

Amyotrophic Lateral Sclerosis and CHARGE syndrome are complex neurological disorders, which never occurred together in the same family and, to date, no putative correlation between them has been described on PubMed Central. Due to our aim was to evaluate the presence of different genetic variants involved in these pathologies, we reported a clinical and genetic description of two sisters affected by these two different disorders. In the CHARGE patient, molecular analysis of the CHD7 gene revealed the c.8016G >A de novo variant in exon 37. The ALS patient had been screened negative for mutations in SOD1, TARDBP, FUS/TLS, C9orf72 and KIF5A genes. Anyway, targeted next generation sequencing analysis identified known and unknown genetic variations in 39 ALS-related genes: a total of 380 variants were reported, of which 194 in the ALS patient and 186 in the CHARGE patient. To date, although the results suggest that the occurrence of the two syndromes in the same family is co-incidental rather than based on a causative genetic variant, we could hypothesize that other factors might act as modulators in the pathogenesis of these different phenotypes.

Published
2018
Full Text
View/download PDF

4. Kinesins in neurological inherited diseases: a novel motor-domain mutation in KIF5A gene in a patient from Southern Italy affected by hereditary spastic paraplegia.

Author

Citrigno L, Magariello A, Pugliese P, Di Palma G, Conforti FL, Petrone A, and Muglia M

Subjects
Female, Humans, Italy, Male, Pedigree, Kinesins genetics, Mutation, Spastic Paraplegia, Hereditary genetics
Abstract

Kinesins are a family of proteins for anterograde transport of the molecules from the neuronal cell body and their impairment has been widely associated with neurodegeneration of the motor neurons. KIF5A gene causes autosomal dominant spastic paraplegia 10, a neurological disorder characterized by spasticity and weakness of the lower limbs (SPG10). We carried out a screening of KIF5A gene in 50 subjects affected by HSP negative to diagnostic test for SPG4, ATL1 and REEP1. We identified a novel variation p.Ile255Met in a 58-year-old man who developed progressive gait disturbance due to spastic paraparesis complicated by axonal neuropathy.

Published
2018
Full Text
View/download PDF

5. Exome sequencing reveals two FA2H mutations in a family with a complicated form of Hereditary Spastic Paraplegia and psychiatric impairments.

Author

Magariello A, Russo C, Citrigno L, Züchner S, Patitucci A, Mazzei R, Conforti FL, Ferlazzo E, Aguglia U, and Muglia M

Subjects
DNA Mutational Analysis, Exome genetics, Humans, Longitudinal Studies, Male, Mental Disorders complications, Middle Aged, Spastic Paraplegia, Hereditary complications, Family Health, Mental Disorders genetics, Mixed Function Oxygenases genetics, Mutation genetics, Spastic Paraplegia, Hereditary genetics
Published
2017
Full Text
View/download PDF

6. ALS-Related Mutant FUS Protein Is Mislocalized to Cytoplasm and Is Recruited into Stress Granules of Fibroblasts from Asymptomatic FUS P525L Mutation Carriers.

Author

Lo Bello M, Di Fini F, Notaro A, Spataro R, Conforti FL, and La Bella V

Subjects
Amyotrophic Lateral Sclerosis physiopathology, Cell Nucleus metabolism, Cells, Cultured, Cytoplasmic Granules metabolism, Female, Follow-Up Studies, Humans, Leucine genetics, Male, Neural Conduction genetics, Proline genetics, Skin cytology, Subcellular Fractions metabolism, Subcellular Fractions pathology, Time Factors, Tubulin metabolism, Amyotrophic Lateral Sclerosis genetics, Amyotrophic Lateral Sclerosis pathology, Fibroblasts metabolism, Mutation genetics, Protein Transport genetics, RNA-Binding Protein FUS genetics
Abstract

Background: Amyotrophic lateral sclerosis (ALS) shows a strong genetic basis, with SOD1, FUS, TARDBP, and C9ORF72 being the genes most frequently involved. This has allowed identification of asymptomatic mutation carriers, which may be of help in understanding the molecular changes preceding disease onset., Objectives: We studied the cellular expression of FUS protein and the effect of heat-shock- and dithiothreitol-induced stress in fibroblasts from FUS P525L mutation carriers, healthy controls, and patients with sporadic ALS., Methods: Western blots and immunocytochemistry were performed to study the subcellular localization of FUS protein. Control and stressed cells were double stained with FUS and the stress marker TIA-R., Results: Fibroblasts from healthy controls and sporadic ALS cases showed a prominent nuclear FUS expression. In the 2 FUS P525L mutation carriers, instead, most cells showed a protein localization in both nucleus and cytoplasm, or exclusively in the cytoplasm. Stress prompted the formation of cytoplasmic granules in all subjects and in sporadic ALS FUS mislocalization to the cytoplasm. Cytoplasmic FUS was recruited into stress granules, which showed a time-dependent decrease in all subjects. However, in the FUS P525L fibroblasts, the granules persisted longer, and they were more numerous than those detected in the cells from controls and sporadic ALS patients., Conclusions: We show that in fibroblasts of FUS P525L mutation carriers, FUS mislocalized to the cytoplasm where it redistributed into stress granules with likely a dose effect, i.e. a higher number of cells with granules, which persist longer, than in controls and ALS cases. These data represent an early molecular change occurring before ALS onset, suggesting a transient preaggregative state., (© 2017 S. Karger AG, Basel.)

Published
2017
Full Text
View/download PDF

7. CHCH10 mutations in an Italian cohort of familial and sporadic amyotrophic lateral sclerosis patients.

Author

Chiò A, Mora G, Sabatelli M, Caponnetto C, Traynor BJ, Johnson JO, Nalls MA, Calvo A, Moglia C, Borghero G, Monsurrò MR, La Bella V, Volanti P, Simone I, Salvi F, Logullo FO, Nilo R, Battistini S, Mandrioli J, Tanel R, Murru MR, Mandich P, Zollino M, Conforti FL, Brunetti M, Barberis M, Restagno G, Penco S, and Lunetta C

Subjects
Aged, Cohort Studies, Female, Frontotemporal Dementia, Humans, Italy, Male, Middle Aged, Amyotrophic Lateral Sclerosis genetics, Genetic Association Studies, Genetic Predisposition to Disease genetics, Mitochondrial Proteins genetics, Mutation
Abstract

Mutations in CHCHD10 have recently been described as a cause of frontotemporal dementia (FTD) comorbid with amyotrophic lateral sclerosis (ALS). The aim of this study was to assess the frequency and clinical characteristics of CHCHD10 mutations in Italian patients diagnosed with familial (n = 64) and apparently sporadic ALS (n = 224). Three apparently sporadic patients were found to carry c.100C>T (p.Pro34Ser) heterozygous variant in the exon 2 of CHCHD10. This mutation had been previously described in 2 unrelated French patients with FTD-ALS. However, our patients had a typical ALS, without evidence of FTD, cerebellar or extrapyramidal signs, or sensorineural deficits. We confirm that CHCHD10 mutations account for ∼ 1% of Italian ALS patients and are a cause of disease in subjects without dementia or other atypical clinical signs., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Published
2015
Full Text
View/download PDF

8. A novel KIF5A mutation in an Italian family marked by spastic paraparesis and congenital deafness.

Author

Muglia M, Citrigno L, D'Errico E, Magariello A, Distaso E, Gasparro AA, Scarafino A, Patitucci A, Conforti FL, Mazzei R, Cortese R, Tortelli R, and Simone IL

Subjects
Adult, DNA Mutational Analysis, Female, Hearing Loss, Sensorineural complications, Humans, Italy, Male, Neurophysiology, Paraparesis, Spastic complications, Family Health, Hearing Loss, Sensorineural genetics, Kinesins genetics, Mutation genetics, Paraparesis, Spastic genetics
Abstract

Hereditary spastic paraplegia (HSP) includes a group of diseases characterized by progressive spastic weakness of the lower limbs (pure forms) with possible additional signs (complicated forms). The SPG10 form is due to alteration in the kinesin1A gene (KIF5A) that encodes the neuronal kinesin heavy chain, a protein required for the anterograde axonal transport. We performed clinical, neurophysiological and molecular studies in two siblings affected by AD-HSP complicated by deafness. The screening of the KIF5A gene revealed the novel mutation p.Leu259Gln in two affected siblings and in their father with a pure form of HSP., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Published
2014
Full Text
View/download PDF

9. Further evidence that DDHD2 gene mutations cause autosomal recessive hereditary spastic paraplegia with thin corpus callosum.

Author

Magariello A, Citrigno L, Zuchner S, Gonzalez M, Patitucci A, Sofia V, Conforti FL, Pappalardo I, Mazzei R, Ungaro C, Zappia M, and Muglia M

Subjects
Family Health, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Corpus Callosum pathology, Mutation genetics, Phospholipases genetics, Spastic Paraplegia, Hereditary genetics, Spastic Paraplegia, Hereditary pathology
Published
2014
Full Text
View/download PDF

10. First mutation in the nuclear localization signal sequence of spastin protein identified in a patient with hereditary spastic paraplegia.

Author

Magariello A, Tortorella C, Patitucci A, Tortelli R, Liguori M, Mazzei R, Conforti FL, Citrigno L, Ungaro C, Simone IL, and Muglia M

Subjects
Brain pathology, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Spastic Paraplegia, Hereditary pathology, Spastin, Adenosine Triphosphatases genetics, Mutation genetics, Spastic Paraplegia, Hereditary genetics
Published
2013
Full Text
View/download PDF

12. FUS mutations in sporadic amyotrophic lateral sclerosis: clinical and genetic analysis.

Author

Sproviero W, La Bella V, Mazzei R, Valentino P, Rodolico C, Simone IL, Logroscino G, Ungaro C, Magariello A, Patitucci A, Tedeschi G, Spataro R, Condino F, Bono F, Citrigno L, Monsurrò MR, Muglia M, Gambardella A, Quattrone A, and Conforti FL

Subjects
Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis pathology, Amyotrophic Lateral Sclerosis physiopathology, DNA Mutational Analysis, Exons genetics, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neurologic Examination, Amyotrophic Lateral Sclerosis genetics, Genetic Predisposition to Disease genetics, Mutation genetics, RNA-Binding Protein FUS genetics
Abstract

Fused in sarcoma (FUS) or translocation in liposarcoma (TLS), a DNA/RNA-binding protein, causes a dominant autosomal inherited form of amyotrophic lateral sclerosis (ALS), ALS 6. Its main role in neurodegeneration is highlighted by the presence of cytoplasmic accumulation of its mutant protein form in ALS patients. To further define the frequency and spectrum of FUS gene mutations, we have performed a molecular screening of a cohort of 327 Italian patients from Southern Italy with sporadic ALS (SALS). We identified 4 patients carrying 3 different missense mutations and several polymorphisms. Two different substitutions occurring in the same amino acidic position have been observed in 2 patients: R521G and R521C respectively; P525L mutation has been found in 2 additional cases. Most of the patients with FUS mutations showed early symptom onset and had short disease survival. We also detected 4 different polymorphic variants (3'-untranslated region [UTR] variant, c.*41G>A; c.523+3ins[GAGGTG]; c.335-15del[TTTT]; and rs13331793) in 9 patients from within our cohort. This study underlines the importance of population-based mutation screening of newly identified genes., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Published
2012
Full Text
View/download PDF

13. Sporadic motor neuron disease in a familial novel SOD1 mutation: incomplete penetrance or chance association?

Author

Conforti FL, Barone R, Fermo SL, Giliberto C, Patti F, Gambardella A, Quattrone A, and Zappia M

Subjects
Aged, 80 and over, Female, Humans, Male, Middle Aged, Motor Neuron Disease pathology, Motor Neuron Disease physiopathology, Pedigree, Superoxide Dismutase-1, Motor Neuron Disease enzymology, Motor Neuron Disease genetics, Mutation, Penetrance, Superoxide Dismutase genetics
Abstract

Cu/Zn superoxide dismutase (SOD1) gene mutations have been reported in familial and sporadic amyotrophic lateral sclerosis (ALS). We report a novel G61R SOD1 mutation in a patient with a distinct phenotype including prominent lower motor neuron dysfunction, proximal weakness and atrophy with asymmetrical onset in the thigh and buttock and relentless clinical course. The G61R mutation segregated in three unaffected relatives including the 80-year-old mother and two of the proband's siblings. Potential mechanisms include an autosomal dominant condition with reduced penetrance or a chance association.

Published
2011
Full Text
View/download PDF

14. Conventional MRI and NOTCH3 gene screening in sporadic CADASIL.

Author

Liguori M, Mazzei R, Ungaro C, Simone IL, Gambardella A, Plasmati I, Fera F, Aguglia U, Lanza P, Bono F, Chiumarulo L, Conforti FL, Consoli D, and Quattrone A

Subjects
Adult, Age of Onset, Aged, Amino Acid Substitution genetics, Brain metabolism, Brain physiopathology, CADASIL physiopathology, Cerebral Arteries metabolism, Cerebral Arteries pathology, Cerebral Arteries physiopathology, Cerebral Hemorrhage diagnosis, Cerebral Hemorrhage genetics, Cerebral Hemorrhage physiopathology, DNA Mutational Analysis, Diffusion Magnetic Resonance Imaging, Female, Gene Frequency genetics, Genetic Markers, Genetic Testing, Genotype, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Receptor, Notch3, Retrospective Studies, Young Adult, Brain pathology, CADASIL diagnosis, CADASIL genetics, Genetic Predisposition to Disease genetics, Mutation genetics, Receptors, Notch genetics
Published
2009
Full Text
View/download PDF

15. A novel Angiogenin gene mutation in a sporadic patient with amyotrophic lateral sclerosis from southern Italy.

Author

Conforti FL, Sprovieri T, Mazzei R, Ungaro C, La Bella V, Tessitore A, Patitucci A, Magariello A, Gabriele AL, Tedeschi G, Simone IL, Majorana G, Valentino P, Condino F, Bono F, Monsurrò MR, Muglia M, and Quattrone A

Subjects
Adult, Aged, Amino Acid Substitution genetics, Amyotrophic Lateral Sclerosis metabolism, Amyotrophic Lateral Sclerosis physiopathology, Chromosome Mapping, Chromosomes, Human, Pair 14 genetics, Cytoprotection genetics, DNA Mutational Analysis, Female, Genetic Linkage genetics, Genetic Markers genetics, Genetic Testing, Humans, Italy, Male, Middle Aged, Motor Neurons pathology, Nerve Degeneration genetics, Nerve Degeneration metabolism, Nerve Degeneration physiopathology, Polymorphism, Single Nucleotide genetics, Ribonuclease, Pancreatic chemistry, Amyotrophic Lateral Sclerosis genetics, Genetic Predisposition to Disease genetics, Motor Neurons metabolism, Mutation genetics, Ribonuclease, Pancreatic genetics
Abstract

Mutations in the Angiogenin gene (ANG) linked to 14q11.2 have been recently discovered to be associated with Amyotrophic Lateral Sclerosis (ALS) in Irish and Scottish populations. In our study we investigated the role of ANG gene in ALS patients from southern Italy. We found a novel mutation in the signal peptide of the ANG gene in a sporadic patient with ALS (SALS). The molecular analysis of the ANG gene also demonstrated an allelic association with the rs11701 single nucleotide polymorphism (SNP) in familial ALS (FALS) but not in SALS patients. Our finding supports the evidence that the ANG gene is involved in ALS.

Published
2008
Full Text
View/download PDF

16. Sporadic ALS is not associated with VAPB gene mutations in Southern Italy.

Author

Conforti FL, Sprovieri T, Mazzei R, Ungaro C, Tessitore A, Tedeschi G, Patitucci A, Magariello A, Gabriele A, Labella V, Simone IL, Majorana G, Monsurrò MR, Valentino P, Muglia M, and Quattrone A

Subjects
Adult, Aged, Aged, 80 and over, Amino Acid Substitution, Aspartic Acid, Base Sequence, Case-Control Studies, Exons, Female, Gene Frequency, Genetic Variation, Glutamic Acid, Humans, Introns, Italy, Male, Middle Aged, Amyotrophic Lateral Sclerosis genetics, Mutation, Vesicular Transport Proteins genetics
Abstract

Mutations in the Cu/Zn superoxide dismutase (Sod1) gene have been reported to cause adult-onset autosomal dominant Amyotrophic Lateral Sclerosis (FALS). In sporadic cases (SALS) de novo mutations in the Sod1 gene have occasionally been observed. The recent finding of a mutation in the VAMP/synaptobrevin-associated membrane protein B (VAPB) gene as the cause of amyotrophic lateral sclerosis (ALS8), prompted us to investigate the entire coding region of this gene in SALS patients. One hundred twenty-five unrelated patients with adult-onset ALS and 150 healthy sex-age-matched subjects with the same genetic background were analyzed. Genetic analysis for all exons of the VAPB gene by DHPLC revealed 5 variant profiles in 83 out of 125 SALS patients. Direct sequencing of these PCR products revealed 3 nucleotide substitutions. Two of these were found within intron 3 of the gene, harbouring 4 variant DHPLC profiles. The third nucleotide variation (Asp130Glu) was the only substitution present in the coding region of the VAPB gene, and it occurred within exon 4. It was found in three patients out of 125. The frequency of the detected exon variation in the VAPB gene was not significantly different between patients and controls. In conclusion, our study suggests that VAPB mutations are not a common cause of adult-onset SALS.

Published
2006
Full Text
View/download PDF

17. Brachial amyotrophic diplegia associated with a novel SOD1 mutation (L106P).

Author

Valentino P, Conforti FL, Pirritano D, Nisticò R, Mazzei R, Patitucci A, Sprovieri T, Gabriele AL, Muglia M, Clodomiro A, Gambardella A, Zappia M, and Quattrone A

Subjects
Aged, Arm innervation, DNA Mutational Analysis, Disease Progression, Functional Laterality genetics, Humans, Male, Motor Neuron Disease enzymology, Motor Neuron Disease genetics, Motor Neurons enzymology, Motor Neurons pathology, Muscle Weakness enzymology, Muscle Weakness genetics, Muscle Weakness physiopathology, Muscle, Skeletal innervation, Muscle, Skeletal pathology, Muscular Atrophy enzymology, Muscular Atrophy genetics, Neural Conduction genetics, Peripheral Nerves pathology, Peripheral Nerves physiopathology, Reflex, Abnormal genetics, Superoxide Dismutase-1, Arm physiopathology, Motor Neuron Disease physiopathology, Muscle, Skeletal physiopathology, Muscular Atrophy physiopathology, Mutation genetics, Superoxide Dismutase genetics
Published
2005
Full Text
View/download PDF

18. A novel mutation in the CLN1 gene in a patient with juvenile neuronal ceroid lipofuscinosis.

Author

Mazzei R, Conforti FL, Magariello A, Bravaccio C, Militerni R, Gabriele AL, Sampaolo S, Patitucci A, Di Iorio G, Muglia M, and Quattrone A

Subjects
Amino Acid Substitution genetics, Child, Cytoplasmic Granules pathology, Cytoplasmic Granules ultrastructure, DNA Mutational Analysis, Female, Humans, Neuronal Ceroid-Lipofuscinoses pathology, Polymerase Chain Reaction, Skin pathology, Skin ultrastructure, Thiolester Hydrolases, Membrane Proteins genetics, Mutation, Neuronal Ceroid-Lipofuscinoses genetics
Abstract

We describe the clinical, neuropathological and molecular findings from a patient affected with neuronal ceroid lipofuscinosis with a juvenile onset (JNCL). She was a 9-year-old right-handed girl with a normal birth and early developmental milestones. At the age of 4 the early symptoms began. Skin biopsy showed granular osmiophilic deposits (GRODs). Because JNCL with GRODs is caused by mutations in the CNL1 gene, we performed a molecular investigation by direct sequencing of nine exons of the CNL1 gene. This analysis revealed a novel mutation in homozygous form in the exon 7 that caused an aminoacid substitution at codon 222 (Leu --> Pro). Direct sequencing of the exon 7 in both parents showed the same substitution in heterozygous form.

Published
2002
Full Text
View/download PDF

19. Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2.

Author

Bolino A, Muglia M, Conforti FL, LeGuern E, Salih MA, Georgiou DM, Christodoulou K, Hausmanowa-Petrusewicz I, Mandich P, Schenone A, Gambardella A, Bono F, Quattrone A, Devoto M, and Monaco AP

Subjects
Alternative Splicing, Charcot-Marie-Tooth Disease enzymology, Chromosomes, Human, Pair 11 genetics, DNA Mutational Analysis, DNA, Complementary isolation & purification, Humans, Protein Tyrosine Phosphatases, Non-Receptor, Reverse Transcriptase Polymerase Chain Reaction, Charcot-Marie-Tooth Disease etiology, Charcot-Marie-Tooth Disease genetics, Mutation genetics, Protein Tyrosine Phosphatases genetics
Abstract

A gene mutated in Charcot-Marie-Tooth disease type 4B (CMT4B), an autosomal recessive demyelinating neuropathy with myelin outfoldings, has been mapped on chromosome 11q22. Using a positional-cloning strategy, we identified in unrelated CMT4B patients mutations occurring in the gene MTMR2, encoding myotubularin-related protein-2, a dual specificity phosphatase (DSP).

Published
2000
Full Text
View/download PDF

20. Nonisotopic method for accurate detection of (CAG)n repeats causing Huntington disease.

Author

Muglia M, Leone O, Annesi G, Gabriele AL, Imbrogno E, Grandinetti C, Conforti FL, Naso F, and Brancati C

Subjects
Alleles, DNA Primers, Humans, Huntingtin Protein, Huntington Disease diagnosis, Nerve Tissue Proteins, Nuclear Proteins, Silver Nitrate, Staining and Labeling, Huntington Disease genetics, Mutation, Polymerase Chain Reaction methods, Proteins genetics, Repetitive Sequences, Nucleic Acid
Abstract

Huntington disease (HD) is a neurodegenerative disorder caused by an expanded trinucleotide repeat (CAG)n located at the 5' end of the novel IT15 gene. Discovery of this expansion allows the molecular diagnosis of HD by measuring repeat length. We applied a simple nonisotopic method to detect (CAG)n repeats, avoiding both radioactive and Southern transfer analysis. The assay is based on direct visualization of electrophoresed PCR products, after silver nitrate gel staining. Its accurate sizing of HD alleles allows presymptomatic diagnosis of at-risk persons. By avoiding isotopic manipulations, the method is safe and accurate, with no radioactive background bands. Furthermore, because it permits direct allele visualization after gel staining, the method is simple and rapid, allowing allele sizing within hours rather than days.

Published
1996

21. Association of Variants in the SPTLC1 Gene with Juvenile Amyotrophic Lateral Sclerosis

Author

Johnson, JO, Chia, R, Miller, DE, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, AE, Topp, SD, Gibbs, JR, Cookson, MR, Sabir, MS, Dalgard, CL, Troakes, C, Jones, AR, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, IP, Dobson-Stone, C, Kwok, JB, Bonkowski, ES, Palvadeau, R, Tienari, PJ, Morrison, KE, Shaw, PJ, Al-Chalabi, A, Brown, RH, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, IJ, Perlman, SJ, Glass, I, Scott, AI, Shaw, CE, Basak, AN, Landers, JE, Chiò, A, Crawford, TO, Smith, BN, Traynor, BJ, Fallini, C, Gkazi, AS, Scotter, EL, Kenna, KP, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, ten Asbroek, ALMA, McKenna-Yasek, D, McLaughlin, RL, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D’Alfonso, S, Mazzini, L, Comi, GP, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, KL, Nicholson, GA, Leblond-Manry, C, Rouleau, GA, Hardiman, O, Veldink, JH, van den Berg, LH, Pall, H, Turner, MR, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, JD, Ratti, A, Adeleye, A, Soltis, AR, Alba, C, Viollet, C, Bacikova, D, Hupalo, DN, Sukumar, G, Pollard, HB, Wilkerson, MD, Martinez, EM, Ahmed, S, Arepalli, S, Baloh, RH, Bowser, R, Brady, CB, Brice, A, Broach, J, Campbell, RH, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, VE, Dunckley, TL, Eicher, JD, England, BK, Faghri, F, Feldman, E, Floeter, MK, Fratta, P, Geiger, JT, Gerhard, G, Gibson, SB, Hardy, J, Harms, MB, Heiman-Patterson, TD, Hernandez, DG, Jansson, L, Kirby, J, Kowall, NW, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, MacGowan, DJL, Maragakis, NJ, Mouzat, K, Murphy, NA, Myllykangas, L, Nalls, MA, Orrell, RW, Ostrow, LW, Pamphlett, R, Pickering-Brown, S, Pioro, EP, Pletnikova, O, Pliner, HA, Pulst, SM, Ravits, JM, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, JD, Scholz, SW, Sendtner, M, Sidle, KC, Simmons, Z, Singleton, AB, Smith, N, Stone, DJ, Troncoso, JC, Valori, M, Van Damme, P, Van Deerlin, VM, Van Den Bosch, L, Zinman, L, Angelocola, SM, Ausiello, FP, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, TA, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, FL, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D’Errico, E, DeMarco, G, Dubbioso, R, Ferrarese, C, Ferraro, PM, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, FO, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, MG, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, MR, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, Johnson J.O., Chia R., Miller D.E., Li R., Kumaran R., Abramzon Y., Alahmady N., Renton A.E., Topp S.D., Gibbs J.R., Cookson M.R., Sabir M.S., Dalgard C.L., Troakes C., Jones A.R., Shatunov A., Iacoangeli A., Al Khleifat A., Ticozzi N., Silani V., Gellera C., Blair I.P., Dobson-Stone C., Kwok J.B., Bonkowski E.S., Palvadeau R., Tienari P.J., Morrison K.E., Shaw P.J., Al-Chalabi A., Brown R.H., Calvo A., Mora G., Al-Saif H., Gotkine M., Leigh F., Chang I.J., Perlman S.J., Glass I., Scott A.I., Shaw C.E., Basak A.N., Landers J.E., Chio A., Crawford T.O., Smith B.N., Traynor B.J., Fallini C., Gkazi A.S., Scotter E.L., Kenna K.P., Keagle P., Tiloca C., Vance C., Colombrita C., King A., Pensato V., Castellotti B., Baas F., Ten Asbroek A.L.M.A., McKenna-Yasek D., McLaughlin R.L., Polak M., Asress S., Esteban-Perez J., Stevic Z., D'Alfonso S., Mazzini L., Comi G.P., Del Bo R., Ceroni M., Gagliardi S., Querin G., Bertolin C., Van Rheenen W., Rademakers R., Van Blitterswijk M., Lauria G., Duga S., Corti S., Cereda C., Corrado L., Soraru G., Williams K.L., Nicholson G.A., Leblond-Manry C., Rouleau G.A., Hardiman O., Veldink J.H., Van Den Berg L.H., Pall H., Turner M.R., Talbot K., Taroni F., Garcia-Redondo A., Wu Z., Glass J.D., Ratti A., Adeleye A., Soltis A.R., Alba C., Viollet C., Bacikova D., Hupalo D.N., Sukumar G., Pollard H.B., Wilkerson M.D., Martinez E.M., Ahmed S., Arepalli S., Baloh R.H., Bowser R., Brady C.B., Brice A., Broach J., Campbell R.H., Camu W., Cooper-Knock J., Ding J., Drepper C., Drory V.E., Dunckley T.L., Eicher J.D., England B.K., Faghri F., Feldman E., Floeter M.K., Fratta P., Geiger J.T., Gerhard G., Gibson S.B., Hardy J., Harms M.B., Heiman-Patterson T.D., Hernandez D.G., Jansson L., Kirby J., Kowall N.W., Laaksovirta H., Landeck N., Landi F., Le Ber I., Lumbroso S., Macgowan D.J.L., Maragakis N.J., Mouzat K., Murphy N.A., Myllykangas L., Nalls M.A., Orrell R.W., Ostrow L.W., Pamphlett R., Pickering-Brown S., Pioro E.P., Pletnikova O., Pliner H.A., Pulst S.M., Ravits J.M., Rivera A., Robberecht W., Rogaeva E., Rollinson S., Rothstein J.D., Scholz S.W., Sendtner M., Sidle K.C., Simmons Z., Singleton A.B., Smith N., Stone D.J., Troncoso J.C., Valori M., Van Damme P., Van Deerlin V.M., Van Den Bosch L., Zinman L., Angelocola S.M., Ausiello F.P., Barberis M., Bartolomei I., Battistini S., Bersano E., Bisogni G., Borghero G., Brunetti M., Cabona C., Canale F., Canosa A., Cantisani T.A., Capasso M., Caponnetto C., Cardinali P., Carrera P., Casale F., Colletti T., Conforti F.L., Conte A., Conti E., Corbo M., Cuccu S., Dalla Bella E., D'Errico E., Demarco G., Dubbioso R., Ferrarese C., Ferraro P.M., Filippi M., Fini N., Floris G., Fuda G., Gallone S., Gianferrari G., Giannini F., Grassano M., Greco L., Iazzolino B., Introna A., La Bella V., Lattante S., Liguori R., Logroscino G., Logullo F.O., Lunetta C., Mandich P., Mandrioli J., Manera U., Manganelli F., Marangi G., Marinou K., Marrosu M.G., Martinelli I., Messina S., Moglia C., Mosca L., Murru M.R., Origone P., Passaniti C., Petrelli C., Petrucci A., Pozzi S., Pugliatti M., Quattrini A., Ricci C., Riolo G., Riva N., Russo M., Sabatelli M., Salamone P., Salivetto M., Salvi F., Santarelli M., Sbaiz L., Sideri R., Simone I., Simonini C., Spataro R., Tanel R., Tedeschi G., Ticca A., Torriello A., Tranquilli S., Tremolizzo L., Trojsi F., Vasta R., Vacchiano V., Vita G., Volanti P., Zollino M., Zucchi E., Johnson, J. O., Chia, R., Miller, D. E., Li, R., Kumaran, R., Abramzon, Y., Alahmady, N., Renton, A. E., Topp, S. D., Gibbs, J. R., Cookson, M. R., Sabir, M. S., Dalgard, C. L., Troakes, C., Jones, A. R., Shatunov, A., Iacoangeli, A., Al Khleifat, A., Ticozzi, N., Silani, V., Gellera, C., Blair, I. P., Dobson-Stone, C., Kwok, J. B., Bonkowski, E. S., Palvadeau, R., Tienari, P. J., Morrison, K. E., Shaw, P. J., Al-Chalabi, A., Brown, R. H., Calvo, A., Mora, G., Al-Saif, H., Gotkine, M., Leigh, F., Chang, I. J., Perlman, S. J., Glass, I., Scott, A. I., Shaw, C. E., Basak, A. N., Landers, J. E., Chio, A., Crawford, T. O., Smith, B. N., Traynor, B. J., Fallini, C., Gkazi, A. S., Scotter, E. L., Kenna, K. P., Keagle, P., Tiloca, C., Vance, C., Colombrita, C., King, A., Pensato, V., Castellotti, B., Baas, F., Ten Asbroek, A. L. M. A., McKenna-Yasek, D., Mclaughlin, R. L., Polak, M., Asress, S., Esteban-Perez, J., Stevic, Z., D'Alfonso, S., Mazzini, L., Comi, G. P., Del Bo, R., Ceroni, M., Gagliardi, S., Querin, G., Bertolin, C., Van Rheenen, W., Rademakers, R., Van Blitterswijk, M., Lauria, G., Duga, S., Corti, S., Cereda, C., Corrado, L., Soraru, G., Williams, K. L., Nicholson, G. A., Leblond-Manry, C., Rouleau, G. A., Hardiman, O., Veldink, J. H., Van Den Berg, L. H., Pall, H., Turner, M. R., Talbot, K., Taroni, F., Garcia-Redondo, A., Wu, Z., Glass, J. D., Ratti, A., Adeleye, A., Soltis, A. R., Alba, C., Viollet, C., Bacikova, D., Hupalo, D. N., Sukumar, G., Pollard, H. B., Wilkerson, M. D., Martinez, E. M., Ahmed, S., Arepalli, S., Baloh, R. H., Bowser, R., Brady, C. B., Brice, A., Broach, J., Campbell, R. H., Camu, W., Cooper-Knock, J., Ding, J., Drepper, C., Drory, V. E., Dunckley, T. L., Eicher, J. D., England, B. K., Faghri, F., Feldman, E., Floeter, M. K., Fratta, P., Geiger, J. T., Gerhard, G., Gibson, S. B., Hardy, J., Harms, M. B., Heiman-Patterson, T. D., Hernandez, D. G., Jansson, L., Kirby, J., Kowall, N. W., Laaksovirta, H., Landeck, N., Landi, F., Le Ber, I., Lumbroso, S., Macgowan, D. J. L., Maragakis, N. J., Mouzat, K., Murphy, N. A., Myllykangas, L., Nalls, M. A., Orrell, R. W., Ostrow, L. W., Pamphlett, R., Pickering-Brown, S., Pioro, E. P., Pletnikova, O., Pliner, H. A., Pulst, S. M., Ravits, J. M., Rivera, A., Robberecht, W., Rogaeva, E., Rollinson, S., Rothstein, J. D., Scholz, S. W., Sendtner, M., Sidle, K. C., Simmons, Z., Singleton, A. B., Smith, N., Stone, D. J., Troncoso, J. C., Valori, M., Van Damme, P., Van Deerlin, V. M., Van Den Bosch, L., Zinman, L., Angelocola, S. M., Ausiello, F. P., Barberis, M., Bartolomei, I., Battistini, S., Bersano, E., Bisogni, G., Borghero, G., Brunetti, M., Cabona, C., Canale, F., Canosa, A., Cantisani, T. A., Capasso, M., Caponnetto, C., Cardinali, P., Carrera, P., Casale, F., Colletti, T., Conforti, F. L., Conte, A., Conti, E., Corbo, M., Cuccu, S., Dalla Bella, E., D'Errico, E., Demarco, G., Dubbioso, R., Ferrarese, C., Ferraro, P. M., Filippi, M., Fini, N., Floris, G., Fuda, G., Gallone, S., Gianferrari, G., Giannini, F., Grassano, M., Greco, L., Iazzolino, B., Introna, A., La Bella, V., Lattante, S., Liguori, R., Logroscino, G., Logullo, F. O., Lunetta, C., Mandich, P., Mandrioli, J., Manera, U., Manganelli, F., Marangi, G., Marinou, K., Marrosu, M. G., Martinelli, I., Messina, S., Moglia, C., Mosca, L., Murru, M. R., Origone, P., Passaniti, C., Petrelli, C., Petrucci, A., Pozzi, S., Pugliatti, M., Quattrini, A., Ricci, C., Riolo, G., Riva, N., Russo, M., Sabatelli, M., Salamone, P., Salivetto, M., Salvi, F., Santarelli, M., Sbaiz, L., Sideri, R., Simone, I., Simonini, C., Spataro, R., Tanel, R., Tedeschi, G., Ticca, A., Torriello, A., Tranquilli, S., Tremolizzo, L., Trojsi, F., Vasta, R., Vacchiano, V., Vita, G., Volanti, P., Zollino, M., Zucchi, E., Başak, Ayşe Nazlı (ORCID 0000-0001-9257-3540 & YÖK ID 1512), Palvadeau, Robin, Johnson, Janel O., Chia, Ruth, Miller, Danny E., Li, Rachel, Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada, Renton, Alan E., Topp, Simon D., Gibbs, J. Raphael, Cookson, Mark R., Sabir, Marya S., Dalgard, Clifton L., Troakes, Claire, Jones, Ashley R., Shatunov, Aleksey, Lacoangeli, Alfredo, Al Khleifat, Ahmad, Ticozzi, Nicola, Silani, Vincenzo, Gellera, Cinzia, Blair, Ian P., Dobson-Stone, Carol, Kwok, John B., Bonkowski, Emily S., Tienari, Pentti J., Morrison, Karen E., Shaw, Pamela J., Al-Chalabi, Ammar, Jr, Robert H. Brown, Calvo, Andrea, Mora, Gabriele, Al-Saif, Hind, Gotkine, Marc, Leigh, Fawn, Chang, Irene J., Perlman, Seth J., Glass, Ian, Scott, Anna, I., Landers, John E., Chio, Adriano, Crawford, Thomas O., Smith, Bradley N., Traynor, Bryan J., Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM), School of Medicine, Johnson, J, Chia, R, Miller, D, Li, R, Kumaran, R, Abramzon, Y, Alahmady, N, Renton, A, Topp, S, Gibbs, J, Cookson, M, Sabir, M, Dalgard, C, Troakes, C, Jones, A, Shatunov, A, Iacoangeli, A, Al Khleifat, A, Ticozzi, N, Silani, V, Gellera, C, Blair, I, Dobson-Stone, C, Kwok, J, Bonkowski, E, Palvadeau, R, Tienari, P, Morrison, K, Shaw, P, Al-Chalabi, A, Brown, R, Calvo, A, Mora, G, Al-Saif, H, Gotkine, M, Leigh, F, Chang, I, Perlman, S, Glass, I, Scott, A, Shaw, C, Basak, A, Landers, J, Chiò, A, Crawford, T, Smith, B, Traynor, B, Fallini, C, Gkazi, A, Scotter, E, Kenna, K, Keagle, P, Tiloca, C, Vance, C, Colombrita, C, King, A, Pensato, V, Castellotti, B, Baas, F, Ten Asbroek, A, McKenna-Yasek, D, Mclaughlin, R, Polak, M, Asress, S, Esteban-Pérez, J, Stevic, Z, D'Alfonso, S, Mazzini, L, Comi, G, Del Bo, R, Ceroni, M, Gagliardi, S, Querin, G, Bertolin, C, van Rheenen, W, Rademakers, R, van Blitterswijk, M, Lauria, G, Duga, S, Corti, S, Cereda, C, Corrado, L, Sorarù, G, Williams, K, Nicholson, G, Leblond-Manry, C, Rouleau, G, Hardiman, O, Veldink, J, van den Berg, L, Pall, H, Turner, M, Talbot, K, Taroni, F, García-Redondo, A, Wu, Z, Glass, J, Ratti, A, Adeleye, A, Soltis, A, Alba, C, Viollet, C, Bacikova, D, Hupalo, D, Sukumar, G, Pollard, H, Wilkerson, M, Martinez, E, Ahmed, S, Arepalli, S, Baloh, R, Bowser, R, Brady, C, Brice, A, Broach, J, Campbell, R, Camu, W, Cooper-Knock, J, Ding, J, Drepper, C, Drory, V, Dunckley, T, Eicher, J, England, B, Faghri, F, Feldman, E, Floeter, M, Fratta, P, Geiger, J, Gerhard, G, Gibson, S, Hardy, J, Harms, M, Heiman-Patterson, T, Hernandez, D, Jansson, L, Kirby, J, Kowall, N, Laaksovirta, H, Landeck, N, Landi, F, Le Ber, I, Lumbroso, S, Macgowan, D, Maragakis, N, Mouzat, K, Murphy, N, Myllykangas, L, Nalls, M, Orrell, R, Ostrow, L, Pamphlett, R, Pickering-Brown, S, Pioro, E, Pletnikova, O, Pliner, H, Pulst, S, Ravits, J, Rivera, A, Robberecht, W, Rogaeva, E, Rollinson, S, Rothstein, J, Scholz, S, Sendtner, M, Sidle, K, Simmons, Z, Singleton, A, Smith, N, Stone, D, Troncoso, J, Valori, M, Van Damme, P, Van Deerlin, V, Van Den Bosch, L, Zinman, L, Angelocola, S, Ausiello, F, Barberis, M, Bartolomei, I, Battistini, S, Bersano, E, Bisogni, G, Borghero, G, Brunetti, M, Cabona, C, Canale, F, Canosa, A, Cantisani, T, Capasso, M, Caponnetto, C, Cardinali, P, Carrera, P, Casale, F, Colletti, T, Conforti, F, Conte, A, Conti, E, Corbo, M, Cuccu, S, Dalla Bella, E, D'Errico, E, Demarco, G, Dubbioso, R, Ferrarese, C, Ferraro, P, Filippi, M, Fini, N, Floris, G, Fuda, G, Gallone, S, Gianferrari, G, Giannini, F, Grassano, M, Greco, L, Iazzolino, B, Introna, A, La Bella, V, Lattante, S, Liguori, R, Logroscino, G, Logullo, F, Lunetta, C, Mandich, P, Mandrioli, J, Manera, U, Manganelli, F, Marangi, G, Marinou, K, Marrosu, M, Martinelli, I, Messina, S, Moglia, C, Mosca, L, Murru, M, Origone, P, Passaniti, C, Petrelli, C, Petrucci, A, Pozzi, S, Pugliatti, M, Quattrini, A, Ricci, C, Riolo, G, Riva, N, Russo, M, Sabatelli, M, Salamone, P, Salivetto, M, Salvi, F, Santarelli, M, Sbaiz, L, Sideri, R, Simone, I, Simonini, C, Spataro, R, Tanel, R, Tedeschi, G, Ticca, A, Torriello, A, Tranquilli, S, Tremolizzo, L, Trojsi, F, Vasta, R, Vacchiano, V, Vita, G, Volanti, P, Zollino, M, Zucchi, E, HUS Neurocenter, Department of Neurosciences, Clinicum, Neurologian yksikkö, TRIMM - Translational Immunology Research Program, Pentti Tienari / Principal Investigator, Human Genetics, ARD - Amsterdam Reproduction and Development, ANS - Complex Trait Genetics, Johnson, Janel O, Miller, Danny E, Renton, Alan E, Topp, Simon D, Gibbs, J Raphael, Cookson, Mark R, Sabir, Marya S, Dalgard, Clifton L, Jones, Ashley R, Iacoangeli, Alfredo, Blair, Ian P, Kwok, John B, Bonkowski, Emily S, Tienari, Pentti J, Morrison, Karen E, Shaw, Pamela J, Brown, Robert H, Chang, Irene J, Perlman, Seth J, Scott, Anna I, Shaw, Christopher E, Basak, A Nazli, Landers, John E, Chiò, Adriano, Crawford, Thomas O, Smith, Bradley N, Traynor, Bryan J, Fallini, Claudia, Gkazi, Athina Soragia, Scotter, Emma L, Kenna, Kevin P, Keagle, Pamela, Tiloca, Cinzia, Vance, Caroline, Colombrita, Claudia, King, Andrew, Pensato, Viviana, Castellotti, Barbara, Baas, Frank, Ten Asbroek, Anneloor L M A, McKenna-Yasek, Diane, Mclaughlin, Russell L, Polak, Meraida, Asress, Seneshaw, Esteban-Pérez, Jesú, Stevic, Zorica, D'Alfonso, Sandra, Mazzini, Letizia, Comi, Giacomo P, Del Bo, Roberto, Ceroni, Mauro, Gagliardi, Stella, Querin, Giorgia, Bertolin, Cinzia, van Rheenen, Wouter, Rademakers, Rosa, van Blitterswijk, Marka, Lauria, Giuseppe, Duga, Stefano, Corti, Stefania, Cereda, Cristina, Corrado, Lucia, Sorarù, Gianni, Williams, Kelly L, Nicholson, Garth A, Leblond-Manry, Claire, Rouleau, Guy A, Hardiman, Orla, Veldink, Jan H, van den Berg, Leonard H, Pall, Hardev, Turner, Martin R, Talbot, Kevin, Taroni, Franco, García-Redondo, Alberto, Wu, Zheyang, Glass, Jonathan D, Ratti, Antonia, Adeleye, Adelani, Soltis, Anthony R, Alba, Camille, Viollet, Coralie, Bacikova, Dagmar, Hupalo, Daniel N, Sukumar, Gauthaman, Pollard, Harvey B, Wilkerson, Matthew D, Martinez, Elisa McGrath, Ahmed, Sarah, Arepalli, Sampath, Baloh, Robert H, Bowser, Robert, Brady, Christopher B, Brice, Alexi, Broach, Jame, Campbell, Roy H, Camu, William, Cooper-Knock, John, Ding, Jinhui, Drepper, Carsten, Drory, Vivian E, Dunckley, Travis L, Eicher, John D, England, Bryce K, Faghri, Faraz, Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro, Geiger, Joshua T, Gerhard, Glenn, Gibson, Summer B, Hardy, John, Harms, Matthew B, Heiman-Patterson, Terry D, Hernandez, Dena G, Jansson, Lilja, Kirby, Janine, Kowall, Neil W, Laaksovirta, Hannu, Landeck, Natalie, Landi, Francesco, Le Ber, Isabelle, Lumbroso, Serge, Macgowan, Daniel J L, Maragakis, Nicholas J, Mouzat, Kevin, Murphy, Natalie A, Myllykangas, Liisa, Nalls, Mike A, Orrell, Richard W, Ostrow, Lyle W, Pamphlett, Roger, Pickering-Brown, Stuart, Pioro, Erik P, Pletnikova, Olga, Pliner, Hannah A, Pulst, Stefan M, Ravits, John M, Rivera, Alberto, Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D, Scholz, Sonja W, Sendtner, Michael, Sidle, Katie C, Simmons, Zachary, Singleton, Andrew B, Smith, Nathan, Stone, David J, Troncoso, Juan C, Valori, Miko, Van Damme, Philip, Van Deerlin, Vivianna M, Van Den Bosch, Ludo, Zinman, Lorne, Angelocola, Stefania M, Ausiello, Francesco P, Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bersano, Enrica, Bisogni, Giulia, Borghero, Giuseppe, Brunetti, Maura, Cabona, Corrado, Canale, Fabrizio, Canosa, Antonio, Cantisani, Teresa A, Capasso, Margherita, Caponnetto, Claudia, Cardinali, Patrizio, Carrera, Paola, Casale, Federico, Colletti, Tiziana, Conforti, Francesca L, Conte, Amelia, Conti, Elisa, Corbo, Massimo, Cuccu, Stefania, Dalla Bella, Eleonora, D'Errico, Eustachio, Demarco, Giovanni, Dubbioso, Raffaele, Ferrarese, Carlo, Ferraro, Pilar M, Filippi, Massimo, Fini, Nicola, Floris, Gianluca, Fuda, Giuseppe, Gallone, Salvatore, Gianferrari, Giulia, Giannini, Fabio, Grassano, Maurizio, Greco, Lucia, Iazzolino, Barbara, Introna, Alessandro, La Bella, Vincenzo, Lattante, Serena, Liguori, Rocco, Logroscino, Giancarlo, Logullo, Francesco O, Lunetta, Christian, Mandich, Paola, Mandrioli, Jessica, Manera, Umberto, Manganelli, Fiore, Marangi, Giuseppe, Marinou, Kalliopi, Marrosu, Maria Giovanna, Martinelli, Ilaria, Messina, Sonia, Moglia, Cristina, Mosca, Lorena, Murru, Maria R, Origone, Paola, Passaniti, Carla, Petrelli, Cristina, Petrucci, Antonio, Pozzi, Susanna, Pugliatti, Maura, Quattrini, Angelo, Ricci, Claudia, Riolo, Giulia, Riva, Nilo, Russo, Massimo, Sabatelli, Mario, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo, Simone, Isabella, Simonini, Cecilia, Spataro, Rossella, Tanel, Raffaella, Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio, Trojsi, Francesca, Vasta, Rosario, Vacchiano, Veria, Vita, Giuseppe, Volanti, Paolo, Zollino, Marcella, and Zucchi, Elisabetta

Subjects
Hereditary sensory neuropathy, L-serine, Mutations, Deoxysphingolipids, Accumulation, Enzyme complex, Juvenile amyotrophic lateral sclerosis, Serine C-Palmitoyltransferase, Whole Exome Sequencing, 0302 clinical medicine, Medicine, Family history, Amyotrophic lateral sclerosis, Child, Index case, Exome sequencing, Original Investigation, 0303 health sciences, Neurosciences and neurology, 3. Good health, Child, Preschool, Failure to thrive, Female, medicine.symptom, Life Sciences & Biomedicine, L-SERINE, Comments, Human, Adult, medicine.medical_specialty, Adolescent, Amyotrophic Lateral Sclerosis, Genetic Predisposition to Disease, Humans, Mutation, Young Adult, Clinical Neurology, NO, 03 medical and health sciences, DEOXYSPHINGOLIPIDS, Internal medicine, Exome Sequencing, Online First, Juvenile, Preschool, 030304 developmental biology, ACCUMULATION, Science & Technology, SPTLC1, business.industry, MUTATIONS, Research, 3112 Neurosciences, medicine.disease, HEREDITARY SENSORY NEUROPATHY, juvenile, 3111 Biomedicine, Neurology (clinical), Neurosciences & Neurology, ALS, genetic, business, 030217 neurology & neurosurgery, Amyotrophic Lateral Sclerosi
Abstract

Key Points Question What genetic variants are associated with juvenile amyotrophic lateral sclerosis (ALS)? Findings In this family-based genetic study, exome sequencing was performed in 3 patients diagnosed with juvenile ALS and failure to thrive; this identified de novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient). Variants in SPTLC1 are a known cause of hereditary sensory and autonomic neuropathy, type 1A, and these data extend the phenotype associated with this gene. Meaning De novo variants in the SPTLC1 gene are associated with juvenile ALS, a fatal neurological disorder., This genetic association study identifies genetic variants associated with juvenile amyotrophic lateral sclerosis., Importance Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation. Objective To identify the genetic variants associated with juvenile ALS. Design, Setting, and Participants In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism. Main Outcomes and Measures De novo variants present only in the index case and not in unaffected family members. Results Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway. Conclusions and Relevance These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.

Published
2021

22. Clinical characteristics of patients with familial amyotrophic lateral sclerosis carrying the pathogenic GGGGCC hexanucleotide repeat expansion of C9ORF72

Author

Chiò, A1, Borghero, G, Restagno, G, Mora, G, Drepper, C, Traynor, Bj, Sendtner, M, Brunetti, M, Ossola, I, Calvo, A, Pugliatti, M, Sotgiu, Ma, Murru, Mr, Marrosu, Mg, Marrosu, F, Marinou, K, Mandrioli, J, Sola, P, Caponnetto, C, Mancardi, G, Mandich, P, La Bella, V, Spataro, R, Conte, A, Monsurrò, Mr, Tedeschi, G, Pisano, F, Bartolomei, I, Salvi, F, Lauria Pinter, G, Simone, I, Logroscino, G, Gambardella, A, Quattrone, A, Lunetta, C, Volanti, P, Zollino, M, Penco, S, Battistini, S, Renton, Ae, Majounie, E, Abramzon, Y, Conforti, Fl, Giannini, F, Corbo, M, Sabatelli, M, Moglia, C, Cammarosano, S, Fuda, G, Canosa, A, Gallo, S, Papetti, L, Luigetti, M, Lattante, S, Marangi, G, Colletti, T, Ricci, C, Origone, P, Floris, G, Cannas, A, Piras, V, Parish, Ld, Solinas, G, Ulgheri, L, Ticca, A, Izzo, F, Laiola, A, Trojsi, F., Chiò, A, Borghero, G, Restagno, G, Mora, G, Drepper, C, Traynor, Bj, Sendtner, M, Brunetti, M, Ossola, I, Calvo, A, Pugliatti, M, Sotgiu, Ma, Murru, Mr, Marrosu, Mg, Marrosu, F, Marinou, K, Mandrioli, J, Sola, P, Caponnetto, C, Mancardi, G, Mandich, P, La Bella, V, Spataro, R, Conte, A, Monsurro', Maria Rosaria, Tedeschi, Gioacchino, Pisano, F, Bartolomei, I, Salvi, F, Lauria Pinter, G, Simone, I, Logroscino, G, Gambardella, A, Quattrone, A, Lunetta, C, Volanti, P, Zollino, M, Penco, S, Battistini, S, the ITALSGEN consortium: Moglia, Cristina, Cammarosano, Stefania, Fuda, Giuseppe, Canosa, Antonio, Gallo, Sara, Papetti, Laura, Luigetti, Marco, Lattante, Serena, Marangi, Giuseppe, Colletti, Tiziana, Ricci, Claudia, Origone, Paola, Floris, Gianluca, Cannas, Antonino, Piras, Valeria, Parish, Leslie D, Solinas, Giuliana, Ulgheri, Lucia, Ticca, Anna, Izzo, Francesco, Laiola, Anna, Trojsi, Francesca, Renton, Ae, Majounie, E, Abramzon, Y, Conforti, Fl, Giannini, F, Corbo, M, Sabatelli, M., Chiò, A., Borghero, G., Restagno, G., Mora, G., Drepper, C., Traynor, B., Sendtner, M., Brunetti, M., Ossola, I., Calvo, A., Pugliatti, M., Sotgiu, M., Murru, M., Marrosu, G., Marrosu, F., Marinou, K., Mandrioli, J., Sola, P., Caponnetto, C., Mancardi, G., Mandich, P., LA BELLA, V., Spataro, R., Conte, A., Monsurrò, M., Tedeschi, G., Pisano, F., Bartolomei, I., Salvi, F., Lauria, G., Simone, I., Logroscino, G., Gambardella, A., Quattrone, A., Lunetta, C., Volanti, P., Zollino, M., Penco, S., Battistini, S., the ITALSGEN, C., Renton, A., Majounie, E., Abramzon, Y., Conforti, F., Giannini, F., and Corbo, M.

Subjects
Male, Parents, Pathology, phenotype-genotype correlation, Cohort Studies, 0302 clinical medicine, C9orf72, amyotrophic lateral sclerosi, genetics, Amyotrophic lateral sclerosis, Age of Onset, amyotrophic lateral sclerosis, familial als, C9Orf72, 0303 health sciences, Sex Characteristics, DNA Repeat Expansion, Adult, Age of Onset, Aged, Amyotrophic Lateral Sclerosis, genetics/pathology, Cohort Studies, DNA Repeat Expansion, DNA, genetics, Female, Humans, Italy, Male, Middle Aged, Mutation, genetics, Parents, Pedigree, Phenotype, Proteins, genetics, Sex Characteristics, Survival Analysis, Middle Aged, 3. Good health, Pedigree, Settore MED/26 - NEUROLOGIA, Phenotype, Italy, Settore MED/26 - Neurologia, Female, Frontotemporal dementia, Adult, medicine.medical_specialty, SOD1, Biology, TARDBP, 03 medical and health sciences, Internal medicine, medicine, Humans, 030304 developmental biology, Aged, amyotrophic lateral sclerosis, familial ALS, C9ORF72 gene, phenotype–genotype correlation, C9orf72 Protein, Amyotrophic Lateral Sclerosis, genetics/pathology, Proteins, Original Articles, DNA, medicine.disease, Survival Analysis, Settore BIO/18 - Genetica, familial ALS, C9ORF72 gene, Mutation, Neurology (clinical), Age of onset, Trinucleotide repeat expansion, familial al, 030217 neurology & neurosurgery
Abstract

A large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72, a gene located on chromosome 9p21, has been recently reported to be responsible for 40% of familial amyotrophic lateral sclerosis cases of European ancestry. The aim of the current article was to describe the phenotype of amyotrophic lateral sclerosis cases carrying the expansion by providing a detailed clinical description of affected cases from representative multi-generational kindreds, and by analysing the age of onset, gender ratio and survival in a large cohort of patients with familial amyotrophic lateral sclerosis. We collected DNA and analysed phenotype data for 141 index Italian familial amyotrophic lateral sclerosis cases (21 of Sardinian ancestry) and 41 German index familial amyotrophic lateral sclerosis cases. Pathogenic repeat expansions were detected in 45 (37.5%) patients from mainland Italy, 12 (57.1%) patients of Sardinian ancestry and nine (22.0%) of the 41 German index familial amyotrophic lateral sclerosis cases. The disease was maternally transmitted in 27 (49.1%) pedigrees and paternally transmitted in 28 (50.9%) pedigrees (P = non-significant). On average, children developed disease 7.0 years earlier than their parents [children: 55.8 years (standard deviation 7.9), parents: 62.8 (standard deviation 10.9); P = 0.003]. Parental phenotype influenced the type of clinical symptoms manifested by the child: of the 13 cases where the affected parent had an amyotrophic lateral sclerosis–frontotemporal dementia or frontotemporal dementia, the affected child also developed amyotrophic lateral sclerosis–frontotemporal dementia in nine cases. When compared with patients carrying mutations of other amyotrophic lateral sclerosis-related genes, those with C9ORF72 expansion had commonly a bulbar onset (42.2% compared with 25.0% among non-C9ORF72 expansion cases, P = 0.03) and cognitive impairment (46.7% compared with 9.1% among non-C9ORF72 expansion cases, P = 0.0001). Median survival from symptom onset among cases carrying C9ORF72 repeat expansion was 3.2 years lower than that of patients carrying TARDBP mutations (5.0 years; 95% confidence interval: 3.6–7.2) and longer than those with FUS mutations (1.9 years; 95% confidence interval: 1.7–2.1). We conclude that C9ORF72 hexanucleotide repeat expansions were the most frequent mutation in our large cohort of patients with familial amyotrophic lateral sclerosis of Italian, Sardinian and German ancestry. Together with mutation of SOD1, TARDBP and FUS, mutations of C9ORF72 account for 60% of familial amyotrophic lateral sclerosis in Italy. Patients with C9ORF72 hexanucleotide repeat expansions present some phenotypic differences compared with patients with mutations of other genes or with unknown mutations, namely a high incidence of bulbar-onset disease and comorbidity with frontotemporal dementia. Their pedigrees typically display a high frequency of cases with pure frontotemporal dementia, widening the concept of familial amyotrophic lateral sclerosis. Keywords

Published
2012

23. Genetic counselling in ALS: facts, uncertainties and clinical suggestions

Author

Chio, A., Battistini, Stefania, Calvo, A., Caponnetto, C., Conforti, F. L., Corbo, M., Giannini, Fabio, Mandrioli, J., Mora, G., Sabatelli, M., Ajmone, C., Mastro, E., Pain, D., Mandich, P., Penco, S., Restagno, G., Zollino, M., Surbone, A., Monsurro, M. R., Tedeschi, G., Conte, A., Luigetti, M., Lattante, S., Marangi, G., Volanti, P., Marinou, K., Papetti, L., Lunetta, C., Pintor, G. L., Salvi, F., Bartolomei, I., Quattrone, A., Gambardella, A., Logroscino, G., Simone, I., Pisano, F., Spataro, R., La Bella, V., Colletti, T., Mancardi, G., Origone, P., Sola, P., Borghero, G., Marrosu, F., Marrosu, M. G., Murru, M. R., Floris, G., Cannas, A., Piras, V., Costantino, E., Pani, C., Sotgiu, M. A., Pugliatti, M., Parish, L. D., Cossu, P., Ticca, A., Rodolico, C., Portaro, S., Ricci, Claudia, Moglia, C., Ossola, I., Brunetti, M., Barberis, M., Canosa, A., Cammarosano, S., Bertuzzo, D., Fuda, G., Ilardi, A., Manera, U., Pastore, I., Sproviero, W., Logullo, F., Tanel, R., Chiò, A, Battistini, S, Calvo, A, Caponnetto, C, Conforti, FL, Corbo, M, Giannini, F, Mandrioli, J, Mora, G, Sabatelli, M, Cammarosano, S, Canosa, A, Moglia, C, Ajmone, C, Mastro, E, Pain, D, Mandich, P, Penco, S, Restagno, G, Zollino, M, Surbone, A, Conforti, Fl, Italsgen, Consortium, Among, Collaborator, Tedeschi, Gioacchino, and Surbone, A.

Subjects
medicine.medical_specialty, Genotype, GENETICS, Genetic counseling, Genetic Counseling, Gene mutation, Settore MED/03 - GENETICA MEDICA, medicine, Humans, Genetic Testing, Amyotrophic lateral sclerosis, Genetic discrimination, Psychiatry, Genetic testing, medicine.diagnostic_test, business.industry, Amyotrophic Lateral Sclerosis, medicine.disease, Penetrance, ALS, 3. Good health, Psychiatry and Mental health, Phenotype, Frontotemporal Dementia, Mutation, Surgery, Settore MED/26 - Neurologia, Neurology (clinical), business, Motor neurone disease, Frontotemporal dementia
Abstract

The clinical approach to patients with amyotrophic lateral sclerosis (ALS) has been largely modified by the identification of novel genes, the detection of gene mutations in apparently sporadic patients, and the discovery of the strict genetic and clinical relation between ALS and frontotemporal dementia (FTD). As a consequence, clinicians are increasingly facing the dilemma on how to handle genetic counselling and testing both for ALS patients and their relatives. On the basis of existing literature on genetics of ALS and of other late-onset life-threatening disorders, we propose clinical suggestions to enable neurologists to provide optimal clinical and genetic counselling to patients and families. Genetic testing should be offered to ALS patients who have a first-degree or second-degree relative with ALS, FTD or both, and should be discussed with, but not offered to, all other ALS patients, with special emphasis on its major uncertainties. Presently, genetic testing should not be proposed to asymptomatic at-risk subjects, unless they request it or are enrolled in research programmes. Genetic counselling in ALS should take into account the uncertainties about the pathogenicity and penetrance of some genetic mutations; the possible presence of mutations of different genes in the same individual; the poor genotypic/phenotypic correlation in most ALS genes; and the phenotypic pleiotropy of some genes. Though psychological, social and ethical implications of genetic testing are still relatively unexplored in ALS, we recommend multidisciplinary counselling that addresses all relevant issues, including disclosure of tests results to family members and the risk for genetic discrimination.

Published
2014
Full Text
View/download PDF

24. A novel Angiogenin gene mutation in a sporadic patient with amyotrophic lateral sclerosis from southern Italy

Author

G. Tedeschi, F. Bono, Maria Muglia, Francesca Luisa Conforti, Francesca Condino, A. L. Gabriele, Carmine Ungaro, Isabella Laura Simone, Alessandro Tessitore, M. R. Monsurrò, Alessandra Patitucci, Rosalucia Mazzei, V. La Bella, Angela Magariello, Aldo Quattrone, Paola Valentino, G. Majorana, Teresa Sprovieri, Conforti, F., Sprovieri, T., Mazzei, R., Ungaro, C., LA BELLA, V., Tessitore, A., Patitucci, A., Magariello, A., Gabriele, A., Tedeschi, G., Simone, I., Majorana, G., Valentino, P., Condino, F., Bono, F., Monsurro, M., Muglia, M., Quattrone, A., Conforti, Fl, Sprovieri, T, Mazzei, R, Ungaro, C, LA BELLA, V, Tessitore, Alessandro, Patitucci, A, Magariello, A, Gabriele, Al, Tedeschi, Gioacchino, Simone, Il, Majorana, G, Valentino, P, Condino, F, Bono, F, Monsurro', Maria Rosaria, and Muglia, M

Subjects
Adult, Genetic Markers, Male, Signal peptide, Angiogenin gene, Angiogenin, Genetic Linkage, DNA Mutational Analysis, Single-nucleotide polymorphism, Gene mutation, Biology, Polymorphism, Single Nucleotide, medicine, Humans, SNP, Genetic Predisposition to Disease, Genetic Testing, Allele, Amyotrophic lateral sclerosis, Gene, Genetics (clinical), Aged, Chromosomes, Human, Pair 14, Motor Neurons, Genetics, Amyotrophic Lateral Sclerosis, Chromosome Mapping, Ribonuclease, Pancreatic, Middle Aged, medicine.disease, Association study, Amino Acid Substitution, Italy, Neurology, Cytoprotection, Mutation, Nerve Degeneration, Pediatrics, Perinatology and Child Health, cardiovascular system, Cancer research, Female, Neurology (clinical), ALS, hormones, hormone substitutes, and hormone antagonists
Abstract

Mutations in the Angiogenin gene (ANG) linked to 14q11.2 have been recently discovered to be associated with Amyotrophic Lateral Sclerosis (ALS) in Irish and Scottish populations. In our study we investigated the role of ANG gene in ALS patients from southern Italy. We found a novel mutation in the signal peptide of the ANG gene in a sporadic patient with ALS (SALS). The molecular analysis of the ANG gene also demonstrated an allelic association with the rs11701 single nucleotide polymorphism (SNP) in familial ALS (FALS) but not in SALS patients. Our finding supports the evidence that the ANG gene is involved in ALS.

Published
2008

25. A novel mutation in the CLN1 gene in a patient with juvenile neuronal ceroid lipofuscinosis

Author

Rosalucia Mazzei, Carmela Bravaccio, Francesca Luisa Conforti, Anna L. Gabriele, Alessandra Patitucci, Angela Magariello, Roberto Militerni, Giuseppe Di Iorio, Maria Muglia, Aldo Quattrone, Simone Sampaolo, Mazzei, R, Conforti, Fl, Magariello, A, Bravaccio, C, Militerni, R, Gabriele, Al, Sampaolo, Simone, Patitucci, A, DI IORIO, Giuseppe, Muglia, M, Quattrone, A., Bravaccio, Carmela, Sampaolo, S, and DI IORIO, G

Subjects
DNA Mutational Analysis, Biology, Cytoplasmic Granules, medicine.disease_cause, Polymerase Chain Reaction, law.invention, Exon, Neuronal Ceroid-Lipofuscinoses, law, vJNCL/GROD, medicine, Humans, Child, Gene, Polymerase chain reaction, Skin, Genetics, Mutation, medicine.diagnostic_test, Membrane Proteins, CLN1 gene, medicine.disease, Pathophysiology, Amino Acid Substitution, Neurology, Membrane protein, Skin biopsy, Female, Neuronal ceroid lipofuscinosis, neuronal ceroid lipofuscinosis, Thiolester Hydrolases, Neurology (clinical), palmitoyl-protein thioesterase protein
Abstract

We describe the clinical, neuropathological and molecular findings from a patient affected with neuronal ceroid lipofuscinosis with a juvenile onset (JNCL). She was a 9-year-old right-handed girl with a normal birth and early developmental milestones. At the age of 4 the early symptoms began. Skin biopsy showed granular osmiophilic deposits (GRODs).Because JNCL with GRODs is caused by mutations in the CNL1 gene, we performed a molecular investigation by direct sequencing of nine exons of the CNL1 gene. This analysis revealed a novel mutation in homozygous form in the exon 7 that caused an aminoacid substitution at codon 222 (Leu --> Pro). Direct sequencing of the exon 7 in both parents showed the same substitution in heterozygous form.

Published
2002

26. TARDBP gene mutations in south Italian patients with amyotrophic lateral sclerosis

Author

Antonio Gambardella, V. La Bella, Angela Magariello, Teresa Sprovieri, G. Tedeschi, M. R. Monsurrò, A. L. Gabriele, Aldo Quattrone, Luigi Citrigno, F. Bono, Paola Valentino, William Sproviero, M. Muglia, Rosalucia Mazzei, Carmine Ungaro, Isabella Laura Simone, Francesca Luisa Conforti, Alessandra Patitucci, Conforti, Fl, Sproviero, W, Simone, Il, Mazzei, R, Valentino, P, Ungaro, C, Magariello, A, Patitucci, A, La Bella, V, Sprovieri, T, Tedeschi, Gioacchino, Citrigno, L, Gabriele, Al, Bono, F, Monsurro', Maria Rosaria, Muglia, M, Gambardella, A, and Quattrone, A.

Subjects
Genetics, Male, SOD1, Amyotrophic Lateral Sclerosis, Mutation, Missense, RNA, Biology, Middle Aged, medicine.disease, TARDBP, Molecular biology, DNA-Binding Proteins, Psychiatry and Mental health, Exon, Italy, RNA splicing, Mutation, medicine, Missense mutation, Humans, Surgery, Female, Neurology (clinical), Amyotrophic lateral sclerosis, Gene
Abstract

TAR-DNA-binding protein 43 (TDP-43) has recently been identified as the major pathological protein in abnormal inclusions in neurons and glial cells in sporadic amyotrophic lateral sclerosis (SALS) and SOD1 negative familial cases with amyotrophic lateral sclerosis (FALS). TDP-43 is evolutionarily conserved, consisting of two RNA recognition motifs and a glycine-rich C-terminal domain. It is involved in the regulation of expression and splicing, and in other cellular processes such as microRNA biogenesis, apoptosis and cell division.1 2 Starting in early 2008, dominant mutations in TARDBP gene have been reported by several groups as a primary cause of ALS. To date, a total of 30 mutations of TARDBP have been reported not only in SOD1 -negative FALS cases (∼3%) but also in SALS cases (∼1.5%). All but one of the mutations identified (D169G) reside in exon 6 of the TARDBP gene, which encodes for the C-terminal glycine-rich domain of TDP-43. All of these mutations are dominantly inherited missense changes with the exception of a truncating mutation (Y374X) at the extreme C terminus of the protein.3 In this study, in order to investigate the presence and frequency of TARDBP mutations in a cohort of 310 south Italian patients affected by ALS, we performed a mutational screening of the exon 4 and exon 6 of the gene in SOD1 -negative FALS and SALS patients. …

Published
2010

27. Sporadic ALS is not associated with VAPB gene mutations in Southern Italy

Author

Paola Valentino, Angela Magariello, A. L. Gabriele, Teresa Sprovieri, Francesca Luisa Conforti, Alessandro Tessitore, Carmine Ungaro, Aldo Quattrone, Alessandra Patitucci, G. Majorana, Rosalucia Mazzei, Maria Muglia, Vincenzo Labella, Maria Rosaria Monsurrò, Isabella Laura Simone, Gioacchino Tedeschi, Conforti, Fl, Sprovieri, T, Mazzei, R, Ungaro, C, Tessitore, Alessandro, Tedeschi, Gioacchino, Patitucci, A, Magariello, A, Gabriele, A, Labella, V, Simone, Il, Majorana, G, Monsurro', Maria Rosaria, Valentino, P, Muglia, M, Quattrone, A., FL CONFORTI, T SPROVIERI, L MAZZEI, C UNGANO, A TESSITORE, G TEDESCHI, A PATINUCCI, A MAGARIELLO, A GABRIELE, LA BELLA V, IL SIMONE, G MAJORANA, MR MONSURR, VALENTINO, MMUGLIA, and A QUATTRONE

Subjects
Adult, Male, SOD1, Vesicular Transport Proteins, Glutamic Acid, Biology, Gene mutation, medicine.disease_cause, Genetic analysis, General Biochemistry, Genetics and Molecular Biology, Pharmacology, Toxicology and Pharmaceutics(all), 03 medical and health sciences, Exon, 0302 clinical medicine, Gene Frequency, medicine, Humans, Coding region, General Pharmacology, Toxicology and Pharmaceutics, Gene, Aged, 030304 developmental biology, Medicine(all), Aged, 80 and over, Genetics, Aspartic Acid, 0303 health sciences, Mutation, Base Sequence, Biochemistry, Genetics and Molecular Biology(all), Brief Report, Amyotrophic Lateral Sclerosis, Genetic Variation, Exons, General Medicine, Middle Aged, VAPB, Molecular biology, Introns, 3. Good health, Amino Acid Substitution, Italy, Case-Control Studies, Female, 030217 neurology & neurosurgery
Abstract

Mutations in the Cu/Zn superoxide dismutase (Sod1) gene have been reported to cause adult-onset autosomal dominant Amyotrophic Lateral Sclerosis (FALS). In sporadic cases (SALS) de novo mutations in the Sod1 gene have occasionally been observed. The recent finding of a mutation in the VAMP/synaptobrevin-associated membrane protein B (VAPB) gene as the cause of amyotrophic lateral sclerosis (ALS8), prompted us to investigate the entire coding region of this gene in SALS patients. One hundred twenty-five unrelated patients with adult-onset ALS and 150 healthy sex-age-matched subjects with the same genetic background were analyzed. Genetic analysis for all exons of the VAPB gene by DHPLC revealed 5 variant profiles in 83 out of 125 SALS patients. Direct sequencing of these PCR products revealed 3 nucleotide substitutions. Two of these were found within intron 3 of the gene, harbouring 4 variant DHPLC profiles. The third nucleotide variation (Asp130Glu) was the only substitution present in the coding region of the VAPB gene, and it occurred within exon 4. It was found in three patients out of 125. The frequency of the detected exon variation in the VAPB gene was not significantly different between patients and controls. In conclusion, our study suggests that VAPB mutations are not a common cause of adult-onset SALS.

Published
2006

28. An Italian case of CADASIL with mutation CGC-TCG in codon 1006, exon 19 Notch3 gene

Author

Rl Mazzei, Davide Nicoli, G De Berti, D. Guidetti, Giovanna Cenacchi, M. Brini, Fl Conforti, Giulio Zuccoli, Bruno Casali, Gianandrea Pasquinelli, Teresa Sprovieri, GUIDETTI D, CASALI B, MAZZEI RL, CENACCHI G, DE BERTI G, ZUCCOLI G, NICOLI D, CONFORTI FL, SPROVIERI T, PASQUINELLI G., and BRINI M

Subjects
Pathology, medicine.medical_specialty, Notch3 gene, Mutation, Missense, CADASIL, Receptors, Cell Surface, Dermatology, medicine.disease_cause, Angiopathy, Leukoencephalopathy, Exon, Proto-Oncogene Proteins, medicine, Missense mutation, Humans, RNA, Messenger, Codon, Receptor, Notch3, Family Health, Mutation, Receptors, Notch, business.industry, Reverse Transcriptase Polymerase Chain Reaction, Brain, General Medicine, Exons, Pseudobulbar palsy, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, medicine.anatomical_structure, Dementia, Multi-Infarct, Italy, Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, Basal lamina, Female, Neurology (clinical), business
Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is commonly overlooked or misdiagnosed owing to its recent identification. It is characterized clinically by recurrent cerebral infarcts, usually appearing between the ages of 30 and 50 years, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in approximately one-third of patients. The pathological hallmark of angiopathy is the presence of characteristic granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells. The defective gene in CADASIL is Notch3, which encodes a large transmembrane receptor, and 70% of missense mutations are in exons 3 and 4. Each gene defect leads to either a gain or loss of a cysteine residue in the extracellular N-terminal domain of the molecule. We report the case of a 53-year-old woman admitted to the hospital for transient ischemic attack and stroke-like episodes recurrent since age 43 years. The patient had pseudobulbar palsy, pyramidal signs, and cognitive impairment but not frank dementia. Cerebral MRI showed periventricular diffuse and confluent ischemic lesions. Ultrastructural study revealed an abnormal deposition of granular osmiophilic material (GOM) within the basal lamina in skin capillaries. Direct sequence analysis of the Notch3 gene was performed. Since no mutation was detected in exons 3 and 4, the remaining exons were sequenced and a missense mutation, CGC-TGC in codon 1006 of exon 19 was found. The mutation led to a gain of a cysteine residue. This is the first missense mutation in codon 1006 of exon 19 of the Notch3 gene to be described in Italy and the second reported in the literature.

Published
2003

Catalog

Books, media, physical & digital resources
See catalog results