A family with Stickler syndrome type 2 has a mutation in the COL11A1 gene resulting in the substitution of glycine 97 by valine in alpha 1(XI) collagen
A family with Stickler syndrome type 2 has a mutation in the COL11A1 gene resulting in the substitution of glycine 97 by valine in alpha 1(XI) collagen
复制标题
DOI：
10.1093/hmg/5.9.1339
复制
发表时间：
1996-09-01
影响因子：
3.5
通讯作者：
Snead, MP
中科院分区：
文献类型：
--
作者：
Richards, AJ;Yates, JRW;Snead, MP
Stickler综合征（遗传性关节眼病）是视网膜脱离的最常见遗传原因，也是最常见的常染色体显性遗传性结缔组织发育不良之一。存在临床和基因座异质性，约三分之二的家族与编码II型前胶原（COL 2A 1）的基因相关。患有1型Sticklers综合征的家族具有特征性先天性玻璃体异常，并且在没有重组的情况下与COL 2A 1基因座的标记物相关联。相反，2型变种的家族具有不同的玻璃体视网膜表型，并且不与COL 2A 1基因连锁。XI型胶原蛋白是与V型胶原蛋白相关的数量较少的纤维状胶原蛋白，并且与更丰富的II型胶原蛋白原纤维相关。最近在一个被描述为Stickler综合征的家族中发现了α 2（XI）前胶原基因COL 11 A2的突变，尽管没有眼部受累。在此，我们首次证实了一个完整的2型Stickler综合征（包括玻璃体和视网膜异常）家族与COL 11 A1基因相关，并证实了该突变是由单碱基G->T突变引起的三螺旋结构域97位甘氨酸取代为缬氨酸。这些结果首次证实了XI型胶原是人类玻璃体的重要结构成分，它们也支持了先前的工作，即编码胶原XI的基因突变可以引起Stickler综合征的某些表现，但其中只有COL 11 A1的突变会引起包括玻璃体视网膜特征在内的完整综合征。
Stickler syndrome (hereditary arthro-ophthalmopathy) is the commonest inherited cause of retinal detachment and one of the commonest autosomal dominant connective tissue dysplasias. There is clinical and locus heterogeneity with about two thirds of families linked to the gene encoding type II procollagen (COL2A1). Families with Sticklers syndrome type 1 have a characteristic congenital vitreous anomaly and are linked without recombination to markers at the COL2A1 locus. In contrast families with the type 2 variety have a different vitreo-retinal phenotype and are not linked to the COL2A1 gene. Type XI collagen is a quantitatively minor fibrillar collagen related to type V collagen and associated with the more abundant type II collagen fibrils. A mutation in COL11A2, the gene for alpha 2 (XI) procollagen, has recently been found in a family described as having Stickler syndrome, although there was no ocular involvement. Here we show for the first time that a family with the full Type 2 Stickler syndrome including vitreous and retinal abnormalities is linked to the COL11A1 gene and characterise the mutation as a Glycine to Valine substitution at position 97 of the triple helical domain caused by a single base G-->T mutation. These results are the first to provide confirmation that type XI collagen is an important structural component of human vitreous, They also support previous work suggesting that mutations in the genes encoding collagen XI can give rise to some manifestations of Stickler syndrome, but of these, only mutations in COL11A1 will give the full syndrome including the vitreo-retinal features.