37 results on '"Renieri, Alessandra"'
Search Results
2. MET is a new confirmed gene responsible for familial distal arthrogryposis.
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Maffeo, Debora, Carrer, Anna, Rina, Angela, Adamo, Loredaria, Lo Rizzo, Caterina, Bruttini, Mirella, Renieri, Alessandra, and Mari, Francesca
- Abstract
In this Correspondence, F. Mari and colleagues report a second two-generation family with distal arthrogryposis caused by a mutation in MET tyrosine kinase. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Effects of the Rho GTPase‐activating toxin CNF1 on fibroblasts derived from Rett syndrome patients: A pilot study.
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Cittadini, Camilla, Germinario, Elena Angela Pia, Maroccia, Zaira, Cosentino, Livia, Maselli, Valeria, Gambardella, Lucrezia, Giambenedetti, Massimo, Guidotti, Marco, Travaglione, Sara, Fallerini, Chiara, Renieri, Alessandra, Marcillo, David Israel Escobar, Ricceri, Laura, Fortini, Paola, De Filippis, Bianca, Fiorentini, Carla, and Fabbri, Alessia
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RETT syndrome ,FIBROBLASTS ,CYTOSKELETON ,RHO GTPases ,PILOT projects - Abstract
The bacterial product CNF1, through its action on the Rho GTPases, is emerging as a modulator of crucial signalling pathways involved in selected neurological diseases characterized by mitochondrial dysfunctions. Mitochondrial impairment has been hypothesized to have a key role in paramount mechanisms underlying Rett syndrome (RTT), a severe neurologic rare disorder. CNF1 has been already reported to have beneficial effects in mouse models of RTT. Using human RTT fibroblasts from four patients carrying different mutations, as a reliable disease‐in‐a‐dish model, we explored the cellular and molecular mechanisms, which can underlie the CNF1‐induced amelioration of RTT deficits. We found that CNF1 treatment modulates the Rho GTPases activity of RTT fibroblasts and induces a considerable re‐organization of the actin cytoskeleton, mainly in stress fibres. Mitochondria of RTT fibroblasts show a hyperfused morphology and CNF1 decreases the mitochondrial mass leaving substantially unaltered the mitochondrial dynamic. From a functional perspective, CNF1 induces mitochondrial membrane potential depolarization and activation of AKT in RTT fibroblasts. Given that mitochondrial quality control is altered in RTT, our results are suggestive of a reactivation of the damaged mitochondria removal via mitophagy restoration. These effects can be at the basis of the beneficial effects of CNF1 in RTT. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Expanding the clinical spectrum associated with the PACS1 p.Arg203Trp mutational hot‐spot: Two additional Italian patients.
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Bruno, Lucia Pia, Doddato, Gabriella, Baldassarri, Margherita, Rizzo, Caterina Lo, Resciniti, Sara, Bruttini, Mirella, Mirjam, Lista, Zguro, Kristina, Furini, Simone, Mencarelli, Maria Antonietta, Renieri, Alessandra, and Ariani, Francesca
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- 2023
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5. Vestibular and audiological findings in the Alport syndrome.
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Barozzi, Stefania, Soi, Daniela, Intieri, Elisabetta, Giani, Marisa, Aldè, Mirko, Tonon, Eleonora, Signorini, Lia, Renieri, Alessandra, Fallerini, Chiara, Perin, Paola, Montini, Giovanni, and Ambrosetti, Umberto
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Alport syndrome (AS) is caused by mutations in collagen IV, which is widespread in the basement membranes of many organs, including the kidneys, eyes, and ears. Whereas the effects of collagen IV changes in the cochlea are well known, no changes have been described in the posterior labyrinth. The aim of this study was to investigate both the auditory and the vestibular function of a group of individuals with AS. Seventeen patients, aged 9–52, underwent audiological tests including pure‐tone and speech audiometry, immittance test and otoacoustic emissions and vestibular tests including video head impulse test, rotatory test, and vestibular evoked myogenic potentials. Hearing loss affected 25% of the males and 27.3% of the females with X‐linked AS. It was sensorineural with a cochlear localization and a variable severity. 50% of the males and 45.4% of the females had a hearing impairment in the high‐frequency range. Otoacoustic emissions were absent in about one‐third of the individuals. A peripheral vestibular dysfunction was present in 75% of the males and 45.4% of the females, with no complaints of vertigo or dizziness. The vestibular impairment was compensated and the vestibulo‐ocular reflex asymmetry was more evident in rotatory tests carried out at lower than higher speeds; a vestibular hypofunction was present in all hearing impaired ears although it was also found in subjects with normal hearing. A posterior labyrinth injury should be hypothesized in AS even when the patient does not manifest hearing disorders or evident signs of renal failure. [ABSTRACT FROM AUTHOR]
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- 2020
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6. Aging-associated genes and let-7 microRNAs: a contribution to myogenic program dysregulation in oculopharyngeal muscular dystrophy.
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Cappelletti, Cristina, Galbardi, Barbara, Bruttini, Mirella, Salerno, Franco, Canioni, Eleonora, Pasanisi, Maria Barbara, Rodolico, Carmelo, Brizzi, Teresa, Mora, Marina, Renieri, Alessandra, Maggi, Lorenzo, Bernasconi, Pia, and Mantegazza, Renato
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- 2019
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7. Diagnosis and management in Pitt‐Hopkins syndrome: First international consensus statement.
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Zollino, Marcella, Marangi, Giuseppe, Giurgea, Irina, Whalen, Sandra, Macchiaiolo, Marina, Smigiel, Robert, Thibert, Ronald L., Benoist, Ingrid, Clayton‐Smith, Jill, De Winter, Channa F., Deckers, Stijn, Huisman, Sylvia, Kruisinga, Frea, Menke, Leonie, Hennekam, Raoul C., Kempink, Dagmar, Lamacchia, Vittoria, Renieri, Alessandra, Nordgren, Ann, and Routledge, Sue
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GENETIC disorders ,NEUROLOGICAL disorders ,DISEASE management ,MOLECULAR diagnosis ,DYSAUTONOMIA ,TRANSCRIPTION factors - Abstract
Pitt‐Hopkins syndrome (PTHS) is a neurodevelopmental disorder characterized by intellectual disability, specific facial features, and marked autonomic nervous system dysfunction, especially with disturbances of regulating respiration and intestinal mobility. It is caused by variants in the transcription factor TCF4. Heterogeneity in the clinical and molecular diagnostic criteria and care practices has prompted a group of international experts to establish guidelines for diagnostics and care. For issues, for which there was limited information available in international literature, we collaborated with national support groups and the participants of a syndrome specific international conference to obtain further information. Here, we discuss the resultant consensus, including the clinical definition of PTHS and a molecular diagnostic pathway. Recommendations for managing particular health problems such as dysregulated respiration are provided. We emphasize the need for integration of care for physical and behavioral issues. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimization of diagnostics and care. [ABSTRACT FROM AUTHOR]
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- 2019
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8. De novo microdeletions and point mutations affecting SOX2 in three individuals with intellectual disability but without major eye malformations.
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Dennert, Nicola, Engels, Hartmut, Cremer, Kirsten, Becker, Jessica, Wohlleber, Eva, Albrecht, Beate, Ehret, Julia K., Lüdecke, Hermann‐Josef, Suri, Mohnish, Carignani, Giulia, Renieri, Alessandra, Kukuk, Guido M., Wieland, Thomas, Andrieux, Joris, Strom, Tim M., Wieczorek, Dagmar, Dieux‐Coëslier, Anne, and Zink, Alexander M.
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Loss-of-function mutations and deletions of the SOX2 gene are known to cause uni- and bilateral anophthalmia and microphthalmia as well as related disorders such as anophthalmia-esophageal-genital syndrome. Thus, anophthalmia/microphthalmia is the primary indication for targeted, 'phenotype first' analyses of SOX2. However, SOX2 mutations are also associated with a wide range of non-ocular abnormalities, such as postnatal growth retardation, structural brain anomalies, hypogenitalism, and developmental delay. The present report describes three patients without anophthalmia/microphthalmia and loss-of-function mutations or microdeletions of SOX2 who had been investigated in a 'genotype first' manner due to intellectual disability/developmental delay using whole exome sequencing or chromosomal microarray analyses. This result prompted us to perform SOX2 Sanger sequencing in 192 developmental delay/intellectual disability patients without anophthalmia or microphthalmia. No additional SOX2 loss-of-function mutations were detected in this cohort, showing that SOX2 is clearly not a major cause of intellectual disability without anophthalmia/microphthalmia. In our three patients and four further, reported 'genotype first' SOX2 microdeletion patients, anophthalmia/microphthalmia was present in less than half of the patients. Thus, SOX2 is another example of a gene whose clinical spectrum is broadened by the generation of 'genotype first' findings using hypothesis-free, genome-wide methods. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
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- 2017
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9. Low‐level TP53 mutational load antecedes clonal expansion in chronic lymphocytic leukaemia.
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Pinto, Anna Maria, Papa, Filomena T., Frullanti, Elisa, Meloni, Ilaria, Tita, Rossella, Caselli, Rossella, Fallerini, Chiara, Lopergolo, Diego, Cetta, Francesco, Mencarelli, Maria Antonietta, Bocchia, Monica, Gozzetti, Alessandro, and Renieri, Alessandra
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GENETIC load ,LYMPHOCYTE count ,CHRONIC lymphocytic leukemia ,LEUCOCYTES ,CLONE cells - Abstract
The article offers information on a study related to low-level TP53 mutational load antecedes clonal expansion in chronic lymphocytic leukaemia (CLL). It notes the advent of Whole Exome Sequencing (WES) that has led to discovery of specific gene mutations in clones of CLL patients, affecting prognosis, disease progression and therapeutic response. It notes the detection of TP53 mutations in some patients with acute myeloid leukaemia (AML)/myelodysplastic syndrome.
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- 2019
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10. Recurrent Duplications of 17q12 Associated with Variable Phenotypes.
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Mitchell, Elyse, Douglas, Andrew, Kjaegaard, Susanne, Callewaert, Bert, Vanlander, Arnaud, Janssens, Sandra, Yuen, Amy Lawson, Skinner, Cindy, Failla, Pinella, Alberti, Antonino, Avola, Emanuela, Fichera, Marco, Kibaek, Maria, Digilio, Maria C., Hannibal, Mark C., den Hollander, Nicolette S., Bizzarri, Veronica, Renieri, Alessandra, Mencarelli, Maria Antonietta, and Fitzgerald, Tomas
- Abstract
The ability to identify the clinical nature of the recurrent duplication of chromosome 17q12 has been limited by its rarity and the diverse range of phenotypes associated with this genomic change. In order to further define the clinical features of affected patients, detailed clinical information was collected in the largest series to date (30 patients and 2 of their siblings) through a multi-institutional collaborative effort. The majority of patients presented with developmental delays varying from mild to severe. Though dysmorphic features were commonly reported, patients do not have consistent and recognizable features. Cardiac, ophthalmologic, growth, behavioral, and other abnormalities were each present in a subset of patients. The newly associated features potentially resulting from 17q12 duplication include height and weight above the 95th percentile, cataracts, microphthalmia, coloboma, astigmatism, tracheomalacia, cutaneous mosaicism, pectus excavatum, scoliosis, hypermobility, hypospadias, diverticulum of Kommerell, pyloric stenosis, and pseudohypoparathryoidism. The majority of duplications were inherited with some carrier parents reporting learning disabilities or microcephaly. We identified additional, potentially contributory copy number changes in a subset of patients, including one patient each with 16p11.2 deletion and 15q13.3 deletion. Our data further define and expand the clinical spectrum associated with duplications of 17q12 and provide support for the role of genomic modifiers contributing to phenotypic variability. [ABSTRACT FROM AUTHOR]
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- 2015
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11. Epilepsy in Rett syndrome-Lessons from the Rett networked database.
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Nissenkorn, Andreea, Levy‐Drummer, Rachel S., Bondi, Ori, Renieri, Alessandra, Villard, Laurent, Mari, Francesca, Mencarelli, Maria A., Lo Rizzo, Caterina, Meloni, Ilaria, Pineda, Mercedes, Armstrong, Judith, Clarke, Angus, Bahi‐Buisson, Nadia, Mejaski, Bosnjak Vlatka, Djuric, Milena, Craiu, Dana, Djukic, Alexsandra, Pini, Giorgio, Bisgaard, Anne Marie, and Melegh, Bela
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RETT syndrome ,EPILEPSY research ,X-linked intellectual disabilities ,GENETIC mutation ,SPASMS ,COGNITION disorders - Abstract
Objective Rett syndrome is an X-linked dominant neurodevelopmental disorder caused by mutations in the MECP2 gene, and characterized by cognitive and communicative regression, loss of hand use, and midline hand stereotypies. Epilepsy is a core symptom, but literature is controversial regarding genotype-phenotype correlation. Analysis of data from a large cohort should overcome this shortcoming. Methods Data from the Rett Syndrome Networked Database on 1,248 female patients were included. Data on phenotypic and genotypic parameters, age of onset, severity of epilepsy, and type of seizures were collected. Statistical analysis was done using the IBM SPSS Version 21 software, logistic regression, and Kaplan-Meier survival curves. Results Epilepsy was present in 68.1% of the patients, with uncontrolled seizures in 32.6% of the patients with epilepsy. Mean age of onset of epilepsy was 4.68 ± (standard deviation) 3.5 years. Younger age of onset was correlated to severity of epilepsy (Spearman correlation r = 0.668, p < 0.01). Patients with late truncating deletions had lower prevalence of epilepsy. Compared to them, the p. R133C mutation, associated with a milder Rett phenotype, increased the risk for epilepsy (odds ratio [ OR] 2.46, confidence interval [ CI] 95% 1.3-4.66), but not for severe epilepsy. The p.R255X mutation conferred an increased risk for epilepsy ( OR 2.07, CI 95% 1.2-3.59) as well as for severe epilepsy ( OR 3.4, CI 95% 1.6-7.3). The p.T158M and p.C306C mutations relatively increased the risk for severe epilepsy ( OR 3.09 and 2.69, CI 95% 1.48-6.4 and 1.19-6.05, respectively), but not for epilepsy occurrence. Significance Various mutations in the MECP2 gene have a different influence on epilepsy, unrelated to the severity of the general Rett phenotype. This might suggest a site-specific effect of MeCp2 on epileptic pathways. Further investigation of these mechanisms should promote better understanding of epileptogenesis in Rett syndrome. [ABSTRACT FROM AUTHOR]
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- 2015
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12. Capping of the N-terminus of PSD-95 by calmodulin triggers its postsynaptic release.
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Zhang, Yonghong, Matt, Lucas, Patriarchi, Tommaso, Malik, Zulfiqar A, Chowdhury, Dhrubajyoti, Park, Deborah K, Renieri, Alessandra, Ames, James B, and Hell, Johannes W
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N-terminal residues ,POSTSYNAPTIC density protein ,CALMODULIN ,EXCITATORY amino acid agents ,SYNAPSES ,AMPA receptors ,METHYL aspartate receptors ,NEUROPLASTICITY - Abstract
Postsynaptic density protein-95 ( PSD-95) is a central element of the postsynaptic architecture of glutamatergic synapses. PSD-95 mediates postsynaptic localization of AMPA receptors and NMDA receptors and plays an important role in synaptic plasticity. PSD-95 is released from postsynaptic membranes in response to Ca
2+ influx via NMDA receptors. Here, we show that Ca2+ /calmodulin ( CaM) binds at the N-terminus of PSD-95. Our NMR structure reveals that both lobes of CaM collapse onto a helical structure of PSD-95 formed at its N-terminus (residues 1-16). This N-terminal capping of PSD-95 by CaM blocks palmitoylation of C3 and C5, which is required for postsynaptic PSD-95 targeting and the binding of CDKL5, a kinase important for synapse stability. CaM forms extensive hydrophobic contacts with Y12 of PSD-95. The PSD-95 mutant Y12 E strongly impairs binding to CaM and Ca2+ -induced release of PSD-95 from the postsynaptic membrane in dendritic spines. Our data indicate that CaM binding to PSD-95 serves to block palmitoylation of PSD-95, which in turn promotes Ca2+ -induced dissociation of PSD-95 from the postsynaptic membrane. [ABSTRACT FROM AUTHOR]- Published
- 2014
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13. A novel mutation in LMX1B gene in a newborn with nail‐patella syndrome: Clinical and dermoscopic findings.
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Tognetti, Linda, Baldassarri, Margherita, Fava, Francesca, Provvidenziale, Luca, Cinotti, Elisa, Renieri, Alessandra, and Rubegni, Pietro
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NAILS (Anatomy) ,GENETIC mutation ,PATELLA ,NAIL diseases ,OLDER patients ,SEQUENCE analysis - Abstract
We report on a 3‐month‐old female patient presenting with bilateral anonychia of the thumbnails and hyponychia of the index nails. Clinico‐dermoscopic examination revealed triangular lunulae in all fingernails. Sequence analysis of LMX1B gene identified a novel heterozygous de novo mutation within exon 2, pathogenetic for a nail‐patella syndrome. [ABSTRACT FROM AUTHOR]
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- 2020
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14. Periventricular heterotopia with white matter abnormalities associated with 6p25 deletion.
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Cellini, Elena, Disciglio, Vittoria, Novara, Francesca, Barkovich, James A., Mencarelli, Maria Antonietta, Hayek, Joussef, Renieri, Alessandra, Zuffardi, Orsetta, and Guerrini, Renzo
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- 2012
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15. Creatine transporter defect diagnosed by proton NMR spectroscopy in males with intellectual disability.
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Mencarelli, Maria Antonietta, Tassini, Maria, Pollazzon, Marzia, Vivi, Antonio, Calderisi, Marco, Falco, Michele, Fichera, Marco, Monti, Lucia, Buoni, Sabrina, Mari, Francesca, Engelke, Udo, Wevers, Ron A., Hayek, Joussef, and Renieri, Alessandra
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Creatine deficiency syndrome due to mutations in X-linked SLC6A8 gene results in nonspecific intellectual disability (ID). Diagnosis cannot be established on clinical grounds and is often based on the assessment of brain creatine levels by magnetic resonance spectroscopy (MRS). Considering high costs of MRS and necessity of sedation, this technique cannot be used as a first level-screening test. Likewise, gene test analysis is time consuming and not easily accessible to all laboratories. In this article feasibility of urine analysis (creatine/creatinine (Cr/Crn) ratio) performed by nuclear magnetic resonance (NMR) as a first level-screening test is explored. Before running a systematic selection of cases a preliminary study for further molecular analysis is shown. NMR urine spectra (n = 1,347) of male patients with an ID without a clinically recognizable syndrome were measured. On the basis of abnormal Cr/Crn ratio, three patients with the highest values were selected for molecular analysis. A confirmatory second urine test was positive in two patients and diagnosis was further confirmed by a decreased brain creatine level and by SLC6A8 gene analysis. A de novo mutation was identified in one. Another patient inherited a novel mutation from the mother who also has a mild ID. A repeat urine test was negative in the third patient and accordingly creatine level in the brain and SLC6A8 gene analysis both gave a normal result. We conclude that Cr/Crn ratio measured by NMR for male patients represents a rapid and useful first level screening test preceding molecular analysis. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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16. Five patients with novel overlapping interstitial deletions in 8q22.2q22.3.
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Kuechler, Alma, Buysse, Karen, Clayton-Smith, Jill, Le Caignec, Cédric, David, Albert, Engels, Hartmut, Kohlhase, Jürgen, Mari, Francesca, Mortier, Geert, Renieri, Alessandra, and Wieczorek, Dagmar
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High-resolution microarray technology has facilitated the detection of submicroscopic chromosome aberrations and characterization of new microdeletion syndromes. We present clinical and molecular data of five patients with previously undescribed overlapping interstitial deletions involving 8q22.2q22.3. All deletions differ in size and breakpoints. Patients 1-4 carry deletions between 5.25 and 6.44 Mb in size, resulting in a minimal deletion overlap of 3.87 Mb (from 100.69 to 104.56 Mb; hg18) comprising at least 25 genes. These patients share similar facial dysmorphisms with blepharophimosis, telecanthus, epicanthus, flat malar region, thin upper lip vermillion, down-turned corners of the mouth, and a poor facial movement/little facial expression. They have a moderate to severe developmental delay (4/4), absent speech (3/4), microcephaly (3/4), a history of seizures (3/4), postnatal short stature (2/4), and a diaphragmatic or hiatal hernia (2/4). Patient 5 was diagnosed with a smaller deletion of about 1.92 Mb (containing nine genes) localized within the deletion overlap of the other four patients. Patient 5 shows a different facial phenotype and a less severe mental retardation. In Patients 1-4, COH1 is involved in the deletion (in total or in part), but none of them showed clinical features of Cohen syndrome. In two patients (Patients 2 and 4), ZFPM2 (also called FOG2, a candidate gene for congenital diaphragmatic hernias) was partly deleted. We suggest that patients with a microdeletion of 8q22.2q22.3 may represent a clinically recognizable condition characterized particularly by the facial phenotype and developmental delay. More patients have to be evaluated to establish a phenotype-genotype correlation. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
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- 2011
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17. Rett syndrome: Revised diagnostic criteria and nomenclature.
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Jeffrey L. Neul, Kaufmann, Walter E., Glaze, Daniel G., Christodoulou, John, Clarke, Angus J., Bahi-Buisson, Nadia, Leonard, Helen, Bailey, Mark E. S., Schanen, N. Carolyn, Zappella, Michele, Renieri, Alessandra, Huppke, Peter, and Percy, Alan K.
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Objective Rett syndrome (RTT) is a severe neurodevelopmental disease that affects approximately 1 in 10,000 live female births and is often caused by mutations in Methyl-CpG-binding protein 2 ( MECP2). Despite distinct clinical features, the accumulation of clinical and molecular information in recent years has generated considerable confusion regarding the diagnosis of RTT. The purpose of this work was to revise and clarify 2002 consensus criteria for the diagnosis of RTT in anticipation of treatment trials. Method RettSearch members, representing the majority of the international clinical RTT specialists, participated in an iterative process to come to a consensus on a revised and simplified clinical diagnostic criteria for RTT. Results The clinical criteria required for the diagnosis of classic and atypical RTT were clarified and simplified. Guidelines for the diagnosis and molecular evaluation of specific variant forms of RTT were developed. Interpretation These revised criteria provide clarity regarding the key features required for the diagnosis of RTT and reinforce the concept that RTT is a clinical diagnosis based on distinct clinical criteria, independent of molecular findings. We recommend that these criteria and guidelines be utilized in any proposed clinical research. Ann Neurol 2010 [ABSTRACT FROM AUTHOR]
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- 2010
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18. Partial silencing of methyl cytosine protein binding 2 (MECP2) in mesenchymal stem cells induces senescence with an increase in damaged DNA.
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Squillaro, Tiziana, Alessio, Nicola, Cipollaro, Marilena, Renieri, Alessandra, Giordano, Antonio, and Galderisi, Umberto
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STEM cells ,PROTEIN binding ,GENE silencing ,DNA ,CELL cycle ,DNA repair - Abstract
DNA methylation is an epigenetic modification that occurs almost exclusively on CpG dinucleotides. MECP2 is a member of a family of proteins that preferentially bind to methylated CpGs. We analyzed the contribution of MECP2 to the physiology of mesenchymal stem cells (MSCs). Partial silencing of MECP2 in human MSCs induced a significant reduction of S-phase cells, along with an increase in G
1 cells. These changes were accompanied by a reduction of apoptosis, the triggering of senescence, a decrease in telomerase activity, and the down-regulation of genes involved in maintaining stem cell properties. Senescence appeared to rely on impairment of DNA damage repair and seemed to occur through RB- and P53-related pathways. The effects of MECP2 silencing could be related to the modification of the DNA methylation status. Our results indicate that the silencing of MECP2 induces an increase in methylated cytosines in the genome. Nevertheless, MECP2 partial silencing did not change the methylation of promoters, whose expression is affected by MECP2 down-regulation. [ABSTRACT FROM AUTHOR]- Published
- 2010
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19. Array comparative genomic hybridization in retinoma and retinoblastoma tissues.
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Sampieri, Katia, Amenduni, Mariangela, Papa, Filomena Tiziana, Katzaki, Eleni, Mencarelli, Maria Antonietta, Marozza, Annabella, Epistolato, Maria Carmela, Toti, Paolo, Lazzi, Stefano, Bruttini, Mirella, De Filippis, Roberta, De Francesco, Sonia, Longo, Ilaria, Meloni, Ilaria, Mari, Francesca, Acquaviva, Antonio, Hadjistilianou, Theodora, Renieri, Alessandra, and Ariani, Francesca
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In retinoblastoma, two RB1 mutations are necessary for tumor development. Recurrent genomic rearrangements may represent subsequent events required for retinoblastoma progression. Array-comparative genomic hybridization was carried out in 18 eye samples, 10 from bilateral and eight from unilateral retinoblastoma patients. Two unilateral cases also showed areas of retinoma. The most frequent imbalance in retinoblastomas was 6p gain (40%), followed by gains at 1q12-q25.3, 2p24.3-p24.2, 9q22.2, and 9q33.1 and losses at 11q24.3, 13q13.2-q22.3, and 16q12.1-q21. Bilateral cases showed a lower number of imbalances than unilateral cases ( P = 0.002). Unilateral cases were divided into low-level (≤4) and high-level (÷7) chromosomal instability groups. The first group presented with younger age at diagnosis (mean 511 days) compared with the second group (mean 1606 days). In one retinoma case ophthalmoscopically diagnosed as a benign lesion no rearrangements were detected, whereas the adjacent retinoblastoma displayed seven aberrations. The other retinoma case identified by retrospective histopathological examination shared three rearrangements with the adjacent retinoblastoma. Two other gene-free rearrangements were retinoma specific. One rearrangement, dup5p, was retinoblastoma specific and included the SKP2 gene. Genomic profiling indicated that the first retinoma was a pretumoral lesion, whereas the other represents a subclone of cells bearing ‘benign’ rearrangements overwhelmed by another subclone presenting aberrations with higher ‘oncogenic’ potential. In summary, the present study shows that bilateral and unilateral retinoblastoma have different chromosomal instability that correlates with the age of tumor onset in unilateral cases. This is the first report of genomic profiling in retinoma tissue, shedding light on the different nature of lesions named ‘retinoma’. ( Cancer Sci 2009; 100: 465–471) [ABSTRACT FROM AUTHOR]
- Published
- 2009
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20. A case report: Bone marrow mesenchymal stem cells from a rett syndrome patient are prone to senescence and show a lower degree of apoptosis.
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Squillaro, Tiziana, Hayek, Giuseppe, Farina, Ernesto, Cipollaro, Marilena, Renieri, Alessandra, and Galderisi, Umberto
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- 2008
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21. Deciphering the underlying genetic and epigenetic events leading to gastric carcinogenesis.
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Vogiatzi, Paraskevi, Vindigni, Carla, Roviello, Franco, Renieri, Alessandra, and Giordano, Antonio
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ADENOCARCINOMA ,GASTRIC diseases ,STOMACH cancer ,CANCER ,PHYSIOLOGY - Abstract
Gastric cancer is a common aggressive malignancy. Although its incidence shows considerable variation among different countries, gastric cancer is still a major health problem worldwide. The causes of stomach cancer are not completely understood. What is clear is that gastric cancer is a multi-stage process involving genetic and epigenetic factors. This review is an in-depth study of the known genetic and epigenetic processes in the development of this tumor, and delineates possible approaches in gene and epigenetic therapy. J. Cell. Physiol. 211: 287–295, 2007. © 2007 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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22. Inheritance of a 38-kb fragment in apparently sporadic facioscapulohumeral muscular dystrophy.
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Vitelli, Francesca, Villanova, Marcello, Malandrini, Alessandro, Bruttini, Mirella, Piccini, Monica, Merlini, Luciano, Guazzi, Giancarlo, Renieri, Alessandra, Vitelli, F, Villanova, M, Malandrini, A, Bruttini, M, Piccini, M, Merlini, L, Guazzi, G, and Renieri, A
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- 1999
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23. Intracellular levels of the LIS1 protein correlate with clinical and neuroradiological findings in patients with classical lissencephaly.
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Fogli, Antonella, Guerrini, Renzo, Moro, Francesca, Fernandez-Alvarez, Emilio, Odile Livet, Marie, Renieri, Alessandra, Cioni, Maddalena, Pilz, Daniela T., Veggiotti, Pierangelo, Rossi, Elena, Ballabio, Andrea, Carrozzo, Romeo, Fogli, A, Guerrini, R, Moro, F, Fernandez-Alvarez, E, Livet, M O, Renieri, A, Cioni, M, and Pilz, D T
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- 1999
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24. Ultrastructural immunocytochemistry of collagenous and non-collagenous proteins in fast-frozen, freeze-substituted, and low-temperature-embedded renal tissue in Alport syndrome.
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Onetti Muda, Andrea, Rahimi, Siavash, Renieri, Alessandra, Rizzoni, Gianfranco, Massella, Laura, and Faraggiana, Tullio
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- 1997
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25. Epstein-barr virus and gastric cancer: Data and unanswered questions.
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Leoncini, Lorenzo, Vindigni, Carla, Megha, Tiziana, Funtò, Ilaria, Pacenti, Lorenzo, Musarò, Mariantonietta, Tosi, Piero, Renieri, Alessandra, Seri, Marco, and Anagnostopoulos, Joannes
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- 1993
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26. Unilateral unifocal advanced intraocular retinoblastoma: is reasonable to adopt intra‐arterial chemotherapy as single therapeutic choice?
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De Francesco, Sonia, Leonini, Sara, Galluzzi, Paolo, Bracco, Sandra, Gennari, Paola, Maria Pinto, Anna, Neri, Giovanni, Barchitta, Matteo, Renieri, Alessandra, and Hadjistilianou, Doris
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RETINOBLASTOMA ,CANCER chemotherapy ,HUMAN chromosome abnormality diagnosis ,GENETIC testing ,DISEASE relapse - Abstract
Purpose: To report the outcome of 30 naive unilateral unifocal retinoblastoma cases treated with intra‐arterial chemotherapy alone. Methods: From 2008 to 2019, 192 eyes affected with retinoblastoma have been treated with intra‐arterial chemotherapy (IAC). 100 out of 192 (52%) eyes were naive advanced unilateral unifocal retinoblastoma (Group B‐E). 30 out of 100 (30%) received intra‐arterial chemotherapy alone. All patients underwent genetic testing at diagnosis. MR was performed at diagnosis, during treatment (when necessary), 3 months after last infusion and annually to evaluate eyeball growth. Results: Tumor control and globe salvage was achieved in 100% of the reported cases (follow‐up ranged from 11 years to 9 months). New tumors or relapse have not been detected. No further local or systemic therapies were necessary. Procedure complications and local and systemic effects are reported. No intraocular or orbital tumor recurrence or metastatic disease have been observed observed. Conclusions: The outcome will be correlated to genetic analysis, doses and drugs used (alone or in combination) and number of infusions received. [ABSTRACT FROM AUTHOR]
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- 2019
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27. Response to Phelan K. et al.: Letter to the Editor Regarding Disciglio et al: Interstitial 22q13 deletions not involving SHANK3 gene: A new contiguous gene syndrome.
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Mari, Francesca, Novelli, Antonio, Romano, Corrado, and Renieri, Alessandra
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- 2015
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28. Superselective ophthalmic artery infusion of melphalan for intraocular retinoblastoma: preliminary results from 140 treatments.
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Venturi, Carlo, Bracco, Sandra, Cerase, Alfonso, Cioni, Samuele, Galluzzi, Paolo, Gennari, Paola, Vallone, Ignazio M., Tinturini, Rebecca, Vittori, Cesare, De Francesco, Sonia, Caini, Mauro, D’Ambrosio, Alfonso, Toti, Paolo, Renieri, Alessandra, and Hadjistilianou, Theodora
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RETINOBLASTOMA ,RETINA cancer ,RETINA ,OPHTHALMIC artery ,CATHETERIZATION ,RETINAL degeneration ,KAPLAN-Meier estimator ,CANCER treatment ,TUMORS - Abstract
. Purpose: To report our experience in superselective ophthalmic artery infusion of melphalan (SOAIM) for intraocular retinoblastoma. Methods: From June 2008 to October 2010, 38 patients (18 women, 20 men; age range at first treatment, 7 months to 22 years) with 41 eyes with retinoblastoma were scheduled for SOAIM, for 17 newly diagnosed retinoblastomas Tumour, Node and Metastasis (TNM) 7th Edition 1a ( n = 1), 1b ( n = 1), 2a ( n = 7), 2b ( n = 4) and 3a ( n = 4) and 24 retinoblastomas with partial remission/relapse TNM 7th Edition 1b ( n = 13), 2a ( n = 1) and 2b ( n = 10). Eight patients (ten eyes) have been treated by SOAIM alone. Follow-up was 6-27 months in 28 patients (30 eyes). Results: Ophthalmic artery cannulation failed in two patients. Thirty-six patients underwent 140 treatments by internal ( n = 112) or external ( n = 28) carotid arteries. No major procedural complications occurred. Two patients have been lost to follow-up. Remaining 34 patients (37 eyes) had no metastatic disease. Four patients suffered permanent ocular complications: chorioretinal dystrophy ( n = 2), ptosis ( n = 1) and strabismus/exotropia ( n = 1). Eight (22%) eyes in eight (24%) patients underwent enucleation: 7/16 (43%) newly diagnosed retinoblastomas and 1/22 (4.5%) retinoblastomas undergoing partial remission/relapse. For all treated eyes, Kaplan-Meier eye enucleation-free rates (K-M) were 85.4% (95% CI, 73.3-97.5%), 74.4% (95% CI, 57-91.8%) and still stable at 6, 12 months and 2 years, respectively. For eyes with partial remission/relapse, and eyes at presentation, K-M at 2 years were 95.5% (95% CI, 86.9-100%) and 45.6% (95% CI, 16.6-74.6%), respectively. Conclusion: Superselective ophthalmic artery infusion of melphalan was safe and powerful, especially following other therapies. Superselective ophthalmic artery infusion of melphalan should be added to focal therapies spectrum. In selected cases, melphalan should be combined with other chemotherapeutic agents. [ABSTRACT FROM AUTHOR]
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- 2013
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29. Interstitial 22q13 deletions not involving SHANK3 gene: a new contiguous gene syndrome.
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Disciglio V, Lo Rizzo C, Mencarelli MA, Mucciolo M, Marozza A, Di Marco C, Massarelli A, Canocchi V, Baldassarri M, Ndoni E, Frullanti E, Amabile S, Anderlid BM, Metcalfe K, Le Caignec C, David A, Fryer A, Boute O, Joris A, Greco D, Pecile V, Battini R, Novelli A, Fichera M, Romano C, Mari F, and Renieri A
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- Child, Child, Preschool, Comparative Genomic Hybridization, Diagnosis, Differential, Facies, Female, Humans, Infant, Male, Phenotype, Syndrome, Chromosome Deletion, Chromosome Disorders diagnosis, Chromosome Disorders genetics, Chromosomes, Human, Pair 22 genetics, Nerve Tissue Proteins genetics
- Abstract
Phelan-McDermid syndrome (22q13.3 deletion syndrome) is a contiguous gene disorder resulting from the deletion of the distal long arm of chromosome 22. SHANK3, a gene within the minimal critical region, is a candidate gene for the major neurological features of this syndrome. We report clinical and molecular data from a study of nine patients with overlapping interstitial deletions in 22q13 not involving SHANK3. All of these deletions overlap with the largest, but not with the smallest deletion associated with Phelan-McDermid syndrome. The deletion sizes and breakpoints varied considerably among our patients, with the largest deletion spanning 6.9 Mb and the smallest deletion spanning 2.7 Mb. Eight out of nine patients had a de novo deletion, while in one patient the origin of deletion was unknown. These patients shared clinical features common to Phelan-McDermid syndrome: developmental delay (11/12), speech delay (11/12), hypotonia (9/12), and feeding difficulties (7/12). Moreover, the majority of patients (8/12) exhibited macrocephaly. In the minimal deleted region, we identified two candidate genes, SULT4A1 and PARVB (associated with the PTEN pathway), which could be associated in our cohort with neurological features and macrocephaly/hypotonia, respectively. This study suggests that the haploinsufficiency of genes in the 22q13 region beside SHANK3 contributes to cognitive and speech development, and that these genes are involved in the phenotype associated with the larger Phelan-McDermid syndrome 22q13 deletions. Moreover, because the deletions in our patients do not involve the SHANK3 gene, we posit the existence of a new contiguous gene syndrome proximal to the smallest terminal deletions in the 22q13 region., (© 2014 Wiley Periodicals, Inc.)
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- 2014
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30. Syndromic mental retardation with thrombocytopenia due to 21q22.11q22.12 deletion: Report of three patients.
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Katzaki E, Morin G, Pollazzon M, Papa FT, Buoni S, Hayek J, Andrieux J, Lecerf L, Popovici C, Receveur A, Mathieu-Dramard M, Renieri A, Mari F, and Philip N
- Subjects
- Adolescent, Child, Child, Preschool, Comparative Genomic Hybridization, Female, Humans, Infant, Infant, Newborn, Male, Pregnancy, Syndrome, Young Adult, Chromosome Deletion, Chromosomes, Human, Pair 21 genetics, Intellectual Disability complications, Intellectual Disability genetics, Thrombocytopenia complications, Thrombocytopenia genetics
- Abstract
During the last few years, an increasing number of microdeletion/microduplication syndromes have been delineated. This rapid evolution is mainly due to the availability of microarray technology as a routine diagnostic tool. Microdeletions of the 21q22.11q22.12 region encompassing the RUNX1 gene have been reported in nine patients presenting with syndromic thrombocytopenia and mental retardation. RUNX1 gene is responsible for an autosomal dominant platelet disorder with predisposition to acute myelogenous leukemia. We report on three novel patients with an overlapping "de novo" interstitial deletion involving the band 21q22 characterized by array-CGH. All our patients presented with severe developmental delay, dysmorphic features, behavioral problems, and thrombocytopenia. Comparing the clinical features of our patients with the overlapping ones already reported two potential phenotypes related to 21q22 microdeletion including RUNX1 were highlighted: thrombocytopenia with +/- mild dysmorphic features and syndromic thrombocytopenia with growth and developmental delay., ((c) 2010 Wiley-Liss, Inc.)
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- 2010
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31. Intellectual disability, midface hypoplasia, facial hypotonia, and Alport syndrome are associated with a deletion in Xq22.3.
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Rodriguez JD, Bhat SS, Meloni I, Ladd S, Leslie ND, Doyne EO, Renieri A, Dupont BR, Stevenson RE, Schwartz CE, and Srivastava AK
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- Child, Preschool, Coenzyme A Ligases genetics, Collagen Type IV genetics, DNA Mutational Analysis, Facies, Female, Humans, In Situ Hybridization, Fluorescence, Language Development Disorders genetics, Male, Pedigree, Phenotype, Abnormalities, Multiple genetics, Chromosome Deletion, Chromosomes, Human, X genetics, Mental Retardation, X-Linked genetics, Nephritis, Hereditary genetics
- Abstract
Alport syndrome with intellectual disability (ID) is a contiguous gene deletion syndrome involving several genes on Xq22.3 including COL4A5 and ACSL4. We report on a family with two males with this disorder and a Xq22.3 deletion. Fluorescent in situ hybridization and genomic analyses mapped the deletion region to between exon 1 of COL4A5 and exon 12 of ACSL4. The patients' mother has microscopic hematuria and was found to be heterozygous for the Xq22.3 deletion. Analysis using reverse transcription polymerase chain reaction of lymphoblastoid cell line RNA from an affected male in the family revealed a stable chimeric transcript with the ACSL4 exons 13-17 replaced by a cryptic exon from intron 1 of the COL4A5 gene. A truncated 54 kDa protein was predicted from this transcript but Western blot analysis and ACSL4 enzyme assay both showed functional nullisomy of ACSL4. We also compared the clinical features of the family with three previously reported families with the ACSL4 gene deletion and found that ID with absent or severely delayed speech, midface hypoplasia, and facial hypotonia are consistent features observed in the absence of ACSL4 gene., ((c) 2010 Wiley-Liss, Inc.)
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- 2010
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32. Cohen syndrome resulting from a novel large intragenic COH1 deletion segregating in an isolated Greek island population.
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Bugiani M, Gyftodimou Y, Tsimpouka P, Lamantea E, Katzaki E, d'Adamo P, Nakou S, Georgoudi N, Grigoriadou M, Tsina E, Kabolis N, Milani D, Pandelia E, Kokotas H, Gasparini P, Giannoulia-Karantana A, Renieri A, Zeviani M, and Petersen MB
- Subjects
- Adolescent, Adult, Child, Cohort Studies, Consanguinity, DNA Mutational Analysis, Developmental Disabilities genetics, Face abnormalities, Female, Geography, Greece, Humans, Male, Microcephaly genetics, Middle Aged, Myopia genetics, Pedigree, Syndrome, Abnormalities, Multiple genetics, Gene Deletion, Intellectual Disability genetics, Vesicular Transport Proteins genetics
- Abstract
Cohen syndrome, caused by mutations in the COH1 gene, is an autosomal recessive disorder consisting of mental retardation, microcephaly, growth delay, severe myopia, progressive chorioretinal dystrophy, facial anomalies, slender limbs with narrow hands and feet, tapered fingers, short stature, kyphosis and/or scoliosis, pectus carinatum, joint hypermobility, pes calcaneovalgus, and, variably, truncal obesity. Here, we describe the clinical and molecular findings in 14 patients from an isolated Greek island population. The clinical phenotype was fairly homogeneous, although microcephaly was not constant, and some patients had severe visual disability. All patients were homozygous for a novel intragenic COH1 deletion spanning exon 6 to exon 16, suggesting a founder effect. The discovery of this mutation has made carrier detection and prenatal diagnosis possible in this population., ((c) 2008 Wiley-Liss, Inc.)
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- 2008
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33. A 3 Mb deletion in 14q12 causes severe mental retardation, mild facial dysmorphisms and Rett-like features.
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Papa FT, Mencarelli MA, Caselli R, Katzaki E, Sampieri K, Meloni I, Ariani F, Longo I, Maggio A, Balestri P, Grosso S, Farnetani MA, Berardi R, Mari F, and Renieri A
- Subjects
- Abnormalities, Multiple genetics, Child, Female, Forkhead Transcription Factors genetics, Humans, Karyotyping, Nerve Tissue Proteins genetics, Oligonucleotide Array Sequence Analysis, Phenotype, Polymerase Chain Reaction, Chromosome Deletion, Chromosomes, Human, Pair 14, Craniofacial Abnormalities genetics, Intellectual Disability genetics, Rett Syndrome genetics
- Abstract
The present report describes a 7-year-old girl with a de novo 3 Mb interstitial deletion of chromosome 14q12, identified by oligo array-CGH. The region is gene poor and contains only five genes two of them, FOXG1B and PRKD1 being deleted also in a previously reported case with a very similar phenotype. Both patients present prominent metopic suture, epicanthic folds, bulbous nasal tip, tented upper lip, everted lower lip and large ears and a clinical course like Rett syndrome, including normal perinatal period, postnatal microcephaly, seizures, and severe mental retardation. FOXG1B (forkhead box G1B) is a very intriguing candidate gene since it is known to promote neuronal progenitor proliferation and to suppress premature neurogenesis and its disruption is reported in a patient with postnatal microcephaly, corpus callosum agenesis, seizures, and severe mental retardation., (Copyright 2008 Wiley-Liss, Inc.)
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- 2008
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34. Delineation of the phenotype associated with 7q36.1q36.2 deletion: long QT syndrome, renal hypoplasia and mental retardation.
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Caselli R, Mencarelli MA, Papa FT, Ariani F, Longo I, Meloni I, Vonella G, Acampa M, Auteri A, Vicari S, Orsi A, Hayek G, Renieri A, and Mari F
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- Adult, Anticonvulsants adverse effects, Base Sequence, Child, DNA Primers genetics, Female, Humans, Male, Maternal-Fetal Exchange, Phenotype, Phenytoin adverse effects, Pregnancy, Syndrome, Chromosome Deletion, Chromosomes, Human, Pair 7 genetics, Intellectual Disability genetics, Kidney abnormalities, Long QT Syndrome genetics
- Abstract
Terminal deletions of the long arm of chromosome 7 are well known and are frequently associated with hypotelorism or holoprosencephaly due to the involvement of the SHH gene located in 7q36.3. These deletions are easily detectable with routine subtelomeric MLPA analysis. Deletions affecting a more proximal part of 7q36, namely bands 7q36.1q36.2 are less common, and may be missed by subtelomeric MLPA analysis. We report a 9-year-old girl with a 5.27 Mb deletion in 7q36.1q36.2, and compare her to literature patients proposing a phenotype characterized by mental retardation, unusual facial features, renal hypoplasia and long QT syndrome due to loss of the KCNH2 gene. These characteristics are sufficiently distinct that the syndrome may be diagnosed on clinical grounds., ((c) 2008 Wiley-Liss, Inc.)
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- 2008
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35. MECP2 deletions and genotype-phenotype correlation in Rett syndrome.
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Scala E, Longo I, Ottimo F, Speciale C, Sampieri K, Katzaki E, Artuso R, Mencarelli MA, D'Ambrogio T, Vonella G, Zappella M, Hayek G, Battaglia A, Mari F, Renieri A, and Ariani F
- Subjects
- Base Sequence, Chromatography, High Pressure Liquid, DNA Primers, Exons, Female, Genotype, Humans, Male, Oligonucleotide Array Sequence Analysis, Pedigree, Phenotype, Polymerase Chain Reaction, Rett Syndrome physiopathology, X Chromosome Inactivation, Gene Deletion, Methyl-CpG-Binding Protein 2 genetics, Rett Syndrome genetics
- Abstract
Rett syndrome is a neurodevelopmental disorder that represents one of the most common genetic causes of mental retardation in girls. MECP2 point mutations in exons 2-4 account for about 80% of classic Rett cases and for a lower percentage of variant patients. We investigated the genetic cause in 77 mutation-negative Rett patients (33 classic, 31 variant, and 13 Rett-like cases) by searching missed MECP2 defects. DHPLC analysis of exon 1 and MLPA analysis allowed us to identify the defect in 17 Rett patients: one exon 1 point mutation (c.47_57del) in a classic case and 16 MECP2 large deletions (15/33 classic and 1/31 variant cases). One identical intragenic MECP2 deletion, probably due to gonadal mosaicism, was found in two sisters with discordant phenotype: one classic and one "highly functioning" preserved speech variant. This result indicates that other epigenetic or genetic factors, beside MECP2, may contribute to phenotype modulation. Three out of 16 MECP2 deletions extend to the adjacent centromeric IRAK1 gene. A putative involvement of the hemizygosity of this gene in the ossification process is discussed. Finally, results reported here clearly indicate that MECP2 large deletions are a common cause of classic Rett, and MLPA analysis is mandatory in MECP2-negative patients, especially in those more severely affected (P = 0.044)., ((c) 2007 Wiley-Liss, Inc.)
- Published
- 2007
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36. Clinical and molecular characterization of a patient with a 2q31.2-32.3 deletion identified by array-CGH.
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Mencarelli MA, Caselli R, Pescucci C, Hayek G, Zappella M, Renieri A, and Mari F
- Subjects
- Craniofacial Abnormalities, Family Health, Humans, Infant, Newborn, Intellectual Disability, Male, Mental Disorders, Oligonucleotide Array Sequence Analysis, Sleep Wake Disorders, Abnormalities, Multiple genetics, Chromosome Deletion, Chromosomes, Human, Pair 2, Nucleic Acid Hybridization
- Abstract
We report on a patient with a de novo interstitial deletion of the long arm of chromosome 2 involving bands 2q31.2-2q32.3. The patient shows severe mental retardation, absence of speech, sleep disturbances, behavioral problems, and some dysmorphic features. In particular, he presents with macrocephaly, high forehead, thick and coarse hair, thick eyebrows, synophrys, increased inner and outer canthal distance, bifid nasal tip, high palate, micrognathia, dysmorphic right ear, and long and tapering fingers. Array-CGH analysis allowed us to identify and characterize a 2q interstitial deletion of about 13 Mb, involving the segment between cytogenetic bands 2q31.2 and 2q32.3. The deletion was confirmed by quantitative PCR. We compare the phenotype of our patient with those already reported in literature. In particular, we discuss the similarities shared with two recently reported patients, studied by array-CGH, who show an overlapping deletion. The common clinical features are: long face, high forehead, abnormal teeth and ears, midface hypoplasia, high palate, micrognathia, transparent and thin skin, high frequency of inguinal hernia, severe development impairment, and behavioral problems. Some genes located in the deleted region may be good candidates for the neurological phenotype such as ZNF533 and MYO1B, which are both involved in neuronal function. Furthermore, the GLS gene could be a good candidate in generating the behavioral phenotype in the patient. In fact, it encodes for the major enzyme yielding glutamate from glutamine and it can be implicated in behavioral disturbances in which glutamate acts as a neurotransmitter., (Copyright 2007 Wiley-Liss, Inc.)
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- 2007
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37. Study of MECP2 gene in Rett syndrome variants and autistic girls.
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Zappella M, Meloni I, Longo I, Canitano R, Hayek G, Rosaia L, Mari F, and Renieri A
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- Adolescent, Autistic Disorder genetics, Child, DNA Mutational Analysis, Female, Genetic Variation, Humans, Intellectual Disability, Methyl-CpG-Binding Protein 2, Speech Disorders genetics, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins genetics, Mutation, Repressor Proteins, Rett Syndrome genetics
- Abstract
Mutations in MECP2 gene account for approximately 80% of cases of Rett syndrome (RTT), an X-linked severe developmental disorder affecting young girls, as well as for most cases of Preserved Speech Variant (PSV), a mild RTT variant in which autistic behavior is common. The aim of this study is to determine whether MECP2 mutations are responsible for PSV only or may cause other forms of autistic disorders. We screened for mutations by SSCP 19 girls with a clinical diagnosis of autism, two of them fulfilling the PSV criteria. A pathogenic mutation was found only in the latter two cases (R133C and R453X). A long follow-up of these two girls revealed a unique clinical course. They initially developed the first three stages of RTT, they were severely retarded and had autistic behavior. Over the years their abilities increased progressively and by early adolescence they lost autistic behavior, becoming adequately accustomed to people and reaching an IQ close to 45. These results confirm previous clinical studies suggesting that a wide spectrum of RTT exists including girls with mental abilities considerably higher than in classic RTT. We conclude that MECP2 mutations (missense or late truncating) can be found in girls with an IQ close to 45 and a clinical history of PSV of Rett syndrome. Furthermore, MECP2 mutations are not found in patients in which autism remains stable over the years., (Copyright 2003 Wiley-Liss, Inc.)
- Published
- 2003
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