Identification of GAA variants through whole exome sequencing targeted to a cohort of 606 patients with unexplained limb-girdle muscle weakness
| العنوان: | Identification of GAA variants through whole exome sequencing targeted to a cohort of 606 patients with unexplained limb-girdle muscle weakness |
|---|---|
| المؤلفون: | Paul Maddison, L. Phillips, Anna Kostera-Pruszczyk, Anna Łusakowska, Ana Töpf, L. Xu, Daniel G. MacArthur, Marta Bertoli, Kristl G. Claeys, Monkol Lek, Ela Akay, Katherine Johnson, Alexandra Bastian, Volker Straub, Stojan Peric, Vidosava Rakocevic Stojanovic, Andreas Hahn |
| المصدر: | Orphanet Journal of Rare Diseases, Vol 12, Iss 1, Pp 1-11 (2017) Orphanet journal of rare diseases 12(1), 173 (2017). doi:10.1186/s13023-017-0722-1 Orphanet Journal of Rare Diseases |
| بيانات النشر: | BMC, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Weakness, Candidate gene, Adolescent, lcsh:Medicine, Biology, Compound heterozygosity, Bioinformatics, Sequence variants, Frameshift mutation, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Exome Sequencing, Glycogen storage disease type II, medicine, Humans, Pharmacology (medical), Child, Genetics (clinical), Exome sequencing, Aged, Aged, 80 and over, Muscle Weakness, Glycogen Storage Disease Type II, Genetic heterogeneity, Research, lcsh:R, Whole exome sequencing, Genetic Variation, Muscle weakness, Pompe disease, alpha-Glucosidases, General Medicine, Middle Aged, medicine.disease, 3. Good health, 030104 developmental biology, Muscular Dystrophies, Limb-Girdle, Child, Preschool, Female, medicine.symptom, 030217 neurology & neurosurgery |
| الوصف: | BACKGROUND: Late-onset Pompe disease is a rare genetic neuromuscular disorder caused by a primary deficiency of α-glucosidase and the associated accumulation of glycogen in lysosomal vacuoles. The deficiency of α-glucosidase can often be detected using an inexpensive and readily accessible dried blood spot test when Pompe disease is suspected. Like several neuromuscular disorders, Pompe disease typically presents with progressive weakness of limb-girdle muscles and respiratory insufficiency. Due to the phenotypic heterogeneity of these disorders, however, it is often difficult for clinicians to reach a diagnosis for patients with Pompe disease. Six hundred and six patients from a European population were recruited onto our study. Inclusion criteria stipulated that index cases must present with limb-girdle weakness or elevated serum creatine kinase activity. Whole exome sequencing with at least 250 ng DNA was completed using an Illumina exome capture and a 38 Mb baited target. A panel of 169 candidate genes for limb-girdle weakness was analysed for disease-causing variants. RESULTS: A total of 35 variants within GAA were detected. Ten distinct variants in eight unrelated index cases (and four siblings not sequenced in our study) were considered disease-causing, with the patients presenting with heterogeneous phenotypes. The eight unrelated individuals were compound heterozygotes for two variants. Six patients carried the intronic splice site c.-13 T > G transversion and two of the six patients also carried the exonic p.Glu176ArgfsTer45 frameshift. Four of the ten variants were novel in their association with Pompe disease. CONCLUSIONS: Here, we highlight the advantage of using whole exome sequencing as a tool for detecting, diagnosing and treating patients with rare, clinically variable genetic disorders. ispartof: Orphanet Journal of Rare Diseases vol:12 issue:1 pages:173-184 ispartof: location:England status: published |
| وصف الملف: | Electronic; application/pdf |
| اللغة: | English |
| تدمد: | 1750-1172 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::11a5bb4bbf80ab971616404ecc7b297cTest http://link.springer.com/article/10.1186/s13023-017-0722-1Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....11a5bb4bbf80ab971616404ecc7b297c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17501172 |
|---|