کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3080675 1189348 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Genotype–phenotype analysis in patients with giant axonal neuropathy (GAN)
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب تکاملی
پیش نمایش صفحه اول مقاله
Genotype–phenotype analysis in patients with giant axonal neuropathy (GAN)
چکیده انگلیسی

Giant axonal neuropathy (GAN, MIM: 256850) is a devastating autosomal recessive disorder characterized by an early onset severe peripheral neuropathy, varying central nervous system involvement and strikingly frizzly hair. Giant axonal neuropathy is usually caused by mutations in the gigaxonin gene (GAN) but genetic heterogeneity has been demonstrated for a milder variant of this disease. Here, we report ten patients referred to us for molecular genetic diagnosis. All patients had typical clinical signs suggestive of giant axonal neuropathy. In seven affected individuals, we found disease causing mutations in the gigaxonin gene affecting both alleles: two splice-site and four missense mutations, not reported previously. Gigaxonin binds N-terminally to ubiquitin activating enzyme E1 and C-terminally to various microtubule associated proteins causing their ubiquitin mediated degradation. It was shown for a number of gigaxonin mutations that they impede this process leading to accumulation of microtubule associated proteins and there by impairing cellular functions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuromuscular Disorders - Volume 17, Issue 8, August 2007, Pages 624–630
نویسندگان
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