کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8282912 1645459 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A novel mutation in FHL1 in a family with X-linked scapuloperoneal myopathy: Phenotypic spectrum and structural study of FHL1 mutations
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
A novel mutation in FHL1 in a family with X-linked scapuloperoneal myopathy: Phenotypic spectrum and structural study of FHL1 mutations
چکیده انگلیسی
An X-linked myopathy was recently associated with mutations in the four-and-a-half-LIM domains 1 (FHL1) gene. We identified a family with late onset, slowly progressive weakness of scapuloperoneal muscles in three brothers and their mother. A novel missense mutation in the LIM2 domain of FHL1 (W122C) co-segregated with disease in the family. The phenotype was less severe than that in other reported families. Muscle biopsy revealed myopathic changes with FHL1 inclusions that were ubiquitin- and desmin-positive. This mutation provides additional evidence for X-linked myopathy caused by a narrow spectrum of mutations in FHL1, mostly in the LIM2 domain. Molecular dynamics (MD) simulations of the newly identified mutation and five previously published missense mutations in the LIM2 domain revealed no major distortions of the protein structure or disruption of zinc binding. There were, however, increases in the nonpolar, solvent-accessible surface area in one or both of two clusters of residues, suggesting that the mutant proteins have a variably increased propensity to aggregate. Review of the literature shows a wide range of phenotypes associated with mutations in FHL1. However, recognizing the typical scapuloperoneal phenotype and X-linked inheritance pattern will help clinicians arrive at the correct diagnosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of the Neurological Sciences - Volume 296, Issues 1–2, 15 September 2010, Pages 22-29
نویسندگان
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