A founder mutation in Anoctamin 5 is a major cause of limb girdle muscular dystrophy
| العنوان: | A founder mutation in Anoctamin 5 is a major cause of limb girdle muscular dystrophy |
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| المؤلفون: | P.J. Hughes, M. C. Walter, Steven H. Laval, Anna Sarkozy, Patrick F. Chinnery, Katrin Koehler, Aleksandar Radunovic, Richard C. Roberts, Sabine Krause, Michelle Eagle, Angela Huebner, Rita Barresi, Geraldine Bailey, Debbie Hicks, J Miller, N. Muelas, Tuomo Polvikoski, Straub, Gavin Hudson, Hanns Lochmüller, K. Bushby |
| المصدر: | Brain. 134:171-182 |
| بيانات النشر: | Oxford University Press (OUP), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Adult, Male, Dysferlinopathy, Weakness, Pathology, medicine.medical_specialty, Population, Anoctamins, Limb girdle, Compound heterozygosity, Polymorphism, Single Nucleotide, Article, Sex Factors, Chloride Channels, Prevalence, medicine, Humans, Respiratory function, Genetic Testing, Muscular dystrophy, Muscle, Skeletal, education, Alleles, Genetics, education.field_of_study, business.industry, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Founder Effect, Muscular Atrophy, Muscular Dystrophies, Limb-Girdle, Mutation, Disease Progression, Female, Neurology (clinical), medicine.symptom, business, Microsatellite Repeats, Limb-girdle muscular dystrophy |
| الوصف: | The limb girdle muscular dystrophies (LGMDs) are a group of disorders with wide genetic and clinical heterogeneity. Recently, mutations in the ANO5 gene, which encodes a putative calcium-activated chloride channel belonging to the Anoctamin family of proteins, were identified in five families with one of two previously identified disorders, LGMD2L and non-dysferlin Miyoshi muscular dystrophy (MMD3). We screened a candidate group of 64 patients from 59 British and German kindreds and found the truncating mutation, c.191dupA in exon 5 of ANO5 in 20 patients, homozygously in 15 and in compound heterozygosity with other ANO5 variants in the rest. An intragenic SNP and an extragenic microsatellite marker are in linkage disequilibrium with the mutation, suggesting a founder effect in the Northern European population. We have further defined the clinical phenotype of ANO5 -associated muscular dystrophy. Patients show adult onset proximal lower limb weakness with highly raised creatinine kinase (CK) values (average 4500 IU/l) and frequent muscle atrophy and asymmetry of muscle involvement. Onset varies from the early 20s to 50s and the weakness is generally slowly progressive, with most patients remaining ambulant for several decades. Distal presentation is much less common but a milder degree of distal lower limb weakness is often observed. Upper limb strength is only mildly affected and cardiac and respiratory function is normal. Females appear less frequently affected. In the North of England population we have identified eight patients with ANO5 mutations, suggesting a minimum prevalence of 0.27/100 000, twice as common as dysferlinopathy. We suggest that mutations in ANO5 represent a relatively common cause of adult onset muscular dystrophy with high CK and that mutation screening, particularly of the common mutation c.191dupA, should be an early step in the diagnostic algorithm of adult LGMD patients. * Abbreviations : CK : creatinine kinase ECG : electrocardiogram EMG : electromyography IHC : immunohistochemistry LGMDs : limb-girdle muscular dystrophy MMD3 : Miyoshi muscular dystrophy MM : Miyoshi myopathy SNP : single-nucleotide polymorphism WB : western blot |
| تدمد: | 1460-2156 0006-8950 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a29389d81d865801a389ed5366a8a28d https://doi.org/10.1093/brain/awq294 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a29389d81d865801a389ed5366a8a28d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602156 00068950 |
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