Marshall syndrome associated with a splicing defect at the COL11A1 locus
Marshall syndrome associated with a splicing defect at the COL11A1 locus
复制标题
DOI：
10.1086/301789
复制
发表时间：
1998-04-01
影响因子：
9.8
通讯作者：
Warman, ML
中科院分区：
文献类型：
--
作者：
Griffith, AJ;Sprunger, LK;Warman, ML
马歇尔综合征是一种罕见的常染色体显性遗传性骨骼发育不良，其表型与更常见的Stickler综合征相似。对于一个大的家族与马歇尔综合征，我们证明了一个剪接供体位点突变的COL 11 A1基因与表型共分离。G（+1）-->A转换导致54-bp外显子的框内跳跃，并从α 1（XI）胶原蛋白多肽的主要三螺旋结构域删除氨基酸726-743。数据支持的假设，α 1（XI）胶原蛋白多肽在骨骼形态发生中的重要作用，延伸到其贡献的软骨细胞外基质的结构完整性。我们的研究结果也证明了马歇尔综合征与与COL 11 A1突变相关的Stickler综合征家族亚群的等位性。
Marshall syndrome is a rare, autosomal dominant skeletal dysplasia that is phenotypically similar to the more common disorder Stickler syndrome. For a large kindred with Marshall syndrome, we demonstrate a splice-donor-site mutation in the COL11A1 gene that cosegregates with the phenotype. The G(+1)-->A transition causes in-frame skipping of a 54-bp exon and deletes amino acids 726-743 from the major triple-helical domain of the alpha 1(XI) collagen polypeptide. The data support the hypothesis that the alpha 1(XI) collagen polypeptide has an important role in skeletal morphogenesis that extends beyond its contribution to structural integrity of the cartilage extracellular matrix. Our results also demonstrate allelism of Marshall syndrome with the subset of Stickler syndrome families associated with COL11A1 mutations.