5 results on '"Paracchini S"'
Search Results
2. Investigation of Dyslexia and SLI Risk Variants in Reading- and Language-Impaired Subjects
- Author
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Newbury, D. F., Paracchini, S., Scerri, T. S., Winchester, L., Addis, L., Richardson, Alex J., Walter, J., Stein, J. F., Talcott, J. B., and Monaco, A. P.
- Published
- 2011
- Full Text
- View/download PDF
3. Putative functional alles of DYX1C1 are not associated with dyslexia susceptibility in a large sample of sibling pairs from the UK.
- Author
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Scerri, T. S., Fisher, S. E., Francks, C., MacPhie, I. L., Paracchini, S., Richardson, A. J., Stein, J. F., and Monaco, A. P.
- Subjects
DYSLEXIA ,LANGUAGE disorders ,READING disability ,COMMUNICATIVE disorders ,GENETICS - Abstract
Cites a study on the association of putative functional alleles of DYX1C1 with dyslexia susceptibility in a Finnish population. Use of trait association analysis to test for a putative effect of the variants; Analysis of alleles associated with dyslexia and with poorer performance for orthographic coding test; Examination of the link of DYX1C1 alleles with better performance in reading related abilities.
- Published
- 2004
- Full Text
- View/download PDF
4. A novel mutation in SPART gene causes a severe neurodevelopmental delay due to mitochondrial dysfunction with complex I impairments and altered pyruvate metabolism
- Author
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Antonia Tranchina, Christian Bergamini, Irene Liparulo, Francesca Bianco, Vito Antonio Baldassarro, Francesco Buscherini, Chiara Diquigiovanni, Luca Masin, Nicola Rizzardi, Romana Fato, Marco Seri, Elena Bonora, Rebeca Diaz, Emanuela Scarano, Duccio Maria Cordelli, Tommaso Pippucci, Silvia Paracchini, Anita Wischmeijer, Diquigiovanni C., Bergamini C., Diaz R., Liparulo I., Bianco F., Masin L., Baldassarro V.A., Rizzardi N., Tranchina A., Buscherini F., Wischmeijer A., Pippucci T., Scarano E., Cordelli D.M., Fato R., Seri M., Paracchini S., Bonora E., University of St Andrews. School of Medicine, University of St Andrews. Centre for Biophotonics, University of St Andrews. Cellular Medicine Division, and University of St Andrews. Biomedical Sciences Research Complex
- Subjects
Male ,0301 basic medicine ,Mitochondrial Diseases ,QH301 Biology ,Cell Cycle Proteins ,Mitochondrion ,medicine.disease_cause ,Biochemistry ,0302 clinical medicine ,Spastic ,Child ,R2C ,Genetics ,Spartin ,Mutation ,~DC~ ,musculoskeletal system ,Mitochondria ,mitochondria ,medicine.symptom ,BDC ,RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry ,Biotechnology ,Spg20 ,Calcium ,Cell Line ,Electron Transport Complex I ,Endosomes ,Humans ,NAD ,NADH Dehydrogenase ,Neurodevelopmental Disorders ,Pyruvates ,NDAS ,QH426 Genetics ,Troyer syndrome ,Short stature ,QH301 ,03 medical and health sciences ,medicine ,QH426 ,Molecular Biology ,Gene ,business.industry ,Muscle weakness ,nervous system diseases ,030104 developmental biology ,RC0321 ,business ,030217 neurology & neurosurgery ,Oxidative stress - Abstract
Loss-of-function mutations in the SPART gene cause Troyer syndrome, a recessive form of spastic paraplegia resulting in muscle weakness, short stature, and cognitive defects. SPART encodes for Spartin, a protein linked to endosomal trafficking and mitochondrial membrane potential maintenance. Here, we identified with whole exome sequencing (WES) a novel frameshift mutation in the SPART gene in 2 brothers presenting an uncharacterized developmental delay and short stature. Functional characterization in an SH-SY5Y cell model shows that this mutation is associated with increased neurite outgrowth. These cells also show a marked decrease in mitochondrial complex I (NADH dehydrogenase) activity, coupled to decreased ATP synthesis and defective mitochondrial membrane potential. The cells also presented an increase in reactive oxygen species, extracellular pyruvate, and NADH levels, consistent with impaired complex I activity. In concordance with a severe mitochondrial failure, Spartin loss also led to an altered intracellular Ca2+ homeostasis that was restored after transient expression of wild-type Spartin. Our data provide for the first time a thorough assessment of Spartin loss effects, including impaired complex I activity coupled to increased extracellular pyruvate. In summary, through a WES study we assign a diagnosis of Troyer syndrome to otherwise undiagnosed patients, and by functional characterization we show that the novel mutation in SPART leads to a profound bioenergetic imbalance.-Diquigiovanni, C., Bergamini, C., Diaz, R., Liparulo, I., Bianco, F., Masin, L., Baldassarro, V. A., Rizzardi, N., Tranchina, A., Buscherini, F., Wischmeijer, A., Pippucci, T., Scarano, E., Cordelli, D. M., Fato, R., Seri, M., Paracchini, S., Bonora, E. A novel mutation in SPART gene causes a severe neurodevelopmental delay due to mitochondrial dysfunction with complex I impairments and altered pyruvate metabolism.
- Published
- 2019
5. Characterization of a family with rare deletions in CNTNAP5 and DOCK4 suggests novel risk loci for autism and dyslexia
- Author
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Wouter G. Staal, Gerd Schulte-Körne, Thomas S. Scerri, Fritz Poustka, Panos Deloukas, Anthony P. Monaco, Roel A. Ophoff, Per Hoffmann, Denise Harold, Anthony J. Bailey, Ernesto Lowy, Kerstin U. Ludwig, Jiannis Ragoussis, Maretha de Jonge, Elena Bacchelli, Michael Conlon O'Donovan, Markus M. Nöthen, Ghazala Mirza, Alistair T. Pagnamenta, Silvia Paracchini, Julie Williams, Elena Maestrini, Andreas G. Chiocchetti, Renske H. Houben, Sabine M. Klauck, Fiorella Minopoli, Jade Chapman, Pagnamenta AT, Bacchelli E, de Jonge MV, Mirza G, Scerri TS, Minopoli F, Chiocchetti A, Ludwig KU, Hoffmann P, Paracchini S, Lowy E, Harold DH, Chapman JA, Klauck SM, Poustka F, Houben RH, Staal WG, Ophoff RA, O'Donovan MC, Williams J, Nöthen MM, Schulte-Körne G, Deloukas P, Ragoussis J, Bailey AJ, Maestrini E, Monaco AP, and International Molecular Genetic Study Of Autism Consortium
- Subjects
Adult ,Male ,Transcription, Genetic ,Cell Adhesion Molecules, Neuronal ,CNV ,CNTNAP5 ,Single-nucleotide polymorphism ,Autistic ,Polymorphism, Single Nucleotide ,Severity of Illness Index ,Dyslexia ,neurexin ,03 medical and health sciences ,0302 clinical medicine ,Reference Values ,mental disorders ,medicine ,SNP ,Missense mutation ,Humans ,Child ,Biological Psychiatry ,030304 developmental biology ,Sequence Deletion ,Genetics ,0303 health sciences ,GTPase-Activating Proteins ,DOCK4 ,DNA ,Middle Aged ,medicine.disease ,Pedigree ,Developmental disorder ,Fusion transcript ,Gene Expression Regulation ,Child Development Disorders, Pervasive ,Case-Control Studies ,Child, Preschool ,Autism ,Female ,Psychology ,030217 neurology & neurosurgery ,SNP array - Abstract
Background: Autism spectrum disorders (ASDs) are characterized by social, communication, and behavioral deficits and complex genetic etiology. A recent study of 517 ASD families implicated DOCK4 by single nucleotide polymorphism (SNP) association and a microdeletion in an affected sibling pair. Methods: The DOCK4 microdeletion on 7q31.1 was further characterized in this family using QuantiSNP analysis of 1M SNP array data and reverse transcription polymerase chain reaction. Extended family members were tested by polymerase chain reaction amplification of junction fragments. DOCK4 dosage was measured in additional samples using SNP arrays. Since QuantiSNP analysis identified a novel CNTNAP5 microdeletion in the same affected sibling pair, this gene was sequenced in 143 additional ASD families. Further polymerase chain reaction-restriction fragment length polymorphism analysis included 380 ASD cases and suitable control subjects. Results: The maternally inherited microdeletion encompassed chr7:110,663,978-111,257,682 and led to a DOCK4-IMMP2L fusion transcript. It was also detected in five extended family members with no ASD. However, six of nine individuals with this microdeletion had poor reading ability, which prompted us to screen 606 other dyslexia cases. This led to the identification of a second DOCK4 microdeletion co-segregating with dyslexia. Assessment of genomic background in the original ASD family detected a paternal 2q14.3 microdeletion disrupting CNTNAP5 that was also transmitted to both affected siblings. Analysis of other ASD cohorts revealed four additional rare missense changes in CNTNAP5. No exonic deletions of DOCK4 or CNTNAP5 were seen in 2091 control subjects. Conclusions: This study highlights two new risk factors for ASD and dyslexia and demonstrates the importance of performing a highresolution assessment of genomic background, even after detection of a rare and likely damaging microdeletion using a targeted approach.
- Published
- 2009
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