دورية أكاديمية
Genotype-phenotype correlations and expansion of the molecular spectrum of AP4M1-related hereditary spastic paraplegia
| العنوان: | Genotype-phenotype correlations and expansion of the molecular spectrum of AP4M1-related hereditary spastic paraplegia |
|---|---|
| المؤلفون: | Bettencourt, C, Salpietro, V, Efthymiou, S, Chelban, V, Hughes, D, Pittman, AM, Federoff, M, Bourinaris, T, Spilioti, M, Deretzi, G, Kalantzakou, T, Houlden, H, Singleton, AB, Xiromerisiou, G |
| المصدر: | Orphanet Journal of Rare Diseases , 12 , Article 172. (2017) |
| بيانات النشر: | BIOMED CENTRAL LTD 21st International Congress of Parkinson's Disease and Movement Disorders |
| سنة النشر: | 2017 |
| المجموعة: | University College London: UCL Discovery |
| مصطلحات موضوعية: | Science & Technology, Life Sciences & Biomedicine, Genetics & Heredity, Medicine, Research & Experimental, Research & Experimental Medicine, Whole exome sequencing, AP4 complex, Epilepsy, Hereditary spastic paraplegia, Cerebellar hypoplasia, DEVELOPMENTAL-DISABILITIES, AUTOSOMAL-DOMINANT, MUTATION, DISORDERS, DISEASE, VARIANTS, FEATURES, GENES, AP4M1 |
| الوصف: | BACKGROUND: Autosomal recessive hereditary spastic paraplegia (HSP) due to AP4M1 mutations is a very rare neurodevelopmental disorder reported for only a few patients. METHODS: We investigated a Greek HSP family using whole exome sequencing (WES). RESULTS: A novel AP4M1A frameshift insertion, and a very rare missense variant were identified in all three affected siblings in the compound heterozygous state (p.V174fs and p.C319R); the unaffected parents were carriers of only one variant. Patients were affected with a combination of: (a) febrile seizures with onset in the first year of life (followed by epileptic non-febrile seizures); (b) distinctive facial appearance (e.g., coarse features, bulbous nose and hypomimia); (c) developmental delay and intellectual disability; (d) early-onset spastic weakness of the lower limbs; and (e) cerebellar hypoplasia/atrophy on brain MRI. CONCLUSIONS: We review genotype-phenotype correlations and discuss clinical overlaps between different AP4-related diseases. The AP4M1 belongs to a complex that mediates vesicle trafficking of glutamate receptors, being likely involved in brain development and neurotransmission. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://discovery.ucl.ac.uk/id/eprint/10037502/1/Houlden_s13023-017-0721-2.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10037502Test/ |
| الإتاحة: | https://discovery.ucl.ac.uk/id/eprint/10037502/1/Houlden_s13023-017-0721-2.pdfTest https://discovery.ucl.ac.uk/id/eprint/10037502Test/ |
| حقوق: | open |
| رقم الانضمام: | edsbas.6C6F5605 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |