Uniparental disomy determined by whole-exome sequencing in a spectrum of rare motoneuron diseases and ataxias
| Autor: | Matthis Synofzik, Jennifer Reichbauer, Rebecca Schüle, Peter De Jonghe, Tim W. Rattay, Ludger Schöls, Stephan Züchner, Anne S. Soehn, Dana M. Bis |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities uniparental disomy Hereditary spastic paraplegia Genetic counseling Biology 03 medical and health sciences 0302 clinical medicine Chromosome 16 Genetics medicine Inheritance Patterns ddc:610 whole exome Molecular Biology Exome Genetics (clinical) Exome sequencing Original Articles medicine.disease Uniparental disomy 3. Good health 030104 developmental biology motoneuron disease Chromosomal region Original Article Ataxia Human medicine 030217 neurology & neurosurgery |
| Zdroj: | Molecular genetics & genomic medicine 5(3), 280-286 (2017). doi:10.1002/mgg3.285 Molecular genetics & genomic medicine Molecular Genetics & Genomic Medicine |
| ISSN: | 2324-9269 |
| DOI: | 10.1002/mgg3.285 |
| Popis: | Background The genetic causes of many rare inherited motoneuron diseases and ataxias (MND and ATX) remain largely unresolved, especially for sporadic patients, despite tremendous advances in gene discovery. Whole exome data is often available for patients, but it is rarely evaluated for unusual inheritance patterns, such as uniparental disomy (UPD). UPD is the inheritance of two copies of a chromosomal region from one parent, which may generate homozygosity for a deleterious recessive variant from only one carrier-parent. Detection of UPD-caused homozygous disease-causing variants is detrimental to accurate genetic counseling. Whole-exome sequencing can allow for the detection of such events. Methods We systematically studied the exomes of a phenotypically heterogeneous cohort of unresolved cases (n = 96 families) to reveal UPD events hindering a diagnosis and to evaluate the prevalence of UPD in recessive MND and ATX. Results One hereditary spastic paraplegia case harbored homozygous regions spanning 80% of chromosome 16. A homozygous disease-causing mutation in the SPG35 disease gene was then identified within this region. Conclusion This study demonstrates the ability to detect UPD in exome data of index patients. Our results suggest that UPD is a rare mechanism for recessive MND and ATX. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text