کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2812426 1569311 2006 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
GDF5 Is a Second Locus for Multiple-Synostosis Syndrome
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی ژنتیک
پیش نمایش صفحه اول مقاله
GDF5 Is a Second Locus for Multiple-Synostosis Syndrome
چکیده انگلیسی

Multiple-synostosis syndrome is an autosomal dominant disorder characterized by progressive symphalangism, carpal/tarsal fusions, deafness, and mild facial dysmorphism. Heterozygosity for functional null mutations in the NOGGIN gene has been shown to be responsible for the disorder. However, in a cohort of six probands with multiple-synostosis syndrome, only one was found to be heterozygous for a NOGGIN mutation (W205X). Linkage studies involving the four-generation family of one of the mutation-negative patients excluded the NOGGIN locus, providing genetic evidence of locus heterogeneity. In this family, polymorphic markers flanking the GDF5 locus were found to cosegregate with the disease, and sequence analysis demonstrated that affected individuals in the family were heterozygous for a novel missense mutation that predicts an R438L substitution in the GDF5 protein. Unlike mutations that lead to haploinsufficiency for GDF5 and produce brachydactyly C, the protein encoded by the multiple-synostosis–syndrome allele was secreted as a mature GDF5 dimer. These data establish locus heterogeneity in multiple-synostosis syndrome and demonstrate that the disorder can result from mutations in either the NOGGIN or the GDF5 gene.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 78, Issue 4, April 2006, Pages 708–712
نویسندگان
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