کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3078861 1189273 2015 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Non-coding VMA21 deletions cause X-linked Myopathy with Excessive Autophagy
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب تکاملی
پیش نمایش صفحه اول مقاله
Non-coding VMA21 deletions cause X-linked Myopathy with Excessive Autophagy
چکیده انگلیسی


• XMEA mutations to date are single-nucleotide changes reducing VMA21 expression.
• We now report 2 new non-coding microdeletions reducing VMA21 expression.
• Both result in a relatively more severe, diffuse, and early onset phenotype.

X-linked Myopathy with Excessive Autophagy (XMEA) affects proximal muscles of the lower extremities and follows a progressive course reminiscent of muscular dystrophy. It is caused by mutations in VMA21 whose protein product assembles lysosomes' proton pumps. All XMEA mutations to date have been single-nucleotide substitutions that reduce VMA21 expression, which leads to modest lysosomal pH increase, the first step in the disease's pathogenesis. We now report a new class of XMEA mutations. We identified two VMA21 non-coding microdeletions, one intronic (c.54-16_54-8del), the other in the 3′UTR (c.*13_*104del). Both resulted in a relatively more severe (early ambulation loss), diffuse (extra-ocular and upper extremity involvement), and early (neonatal) onset disease compared to previously reported patients. Our cases highlight the importance of including non-coding regions of VMA21 in genetic testing panels of dystrophies and myopathies. Specific diagnosis of XMEA will be particularly important as therapies aimed at correcting the modest rise in lysosomal pH at the root of this disease are developed.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuromuscular Disorders - Volume 25, Issue 3, March 2015, Pages 207–211
نویسندگان
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