A Loss of Function Mutation in the COL9A2 Gene Cause Autosomal Recessive Stickler Syndrome
A Loss of Function Mutation in the COL9A2 Gene Cause Autosomal Recessive Stickler Syndrome
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DOI：
10.1002/ajmg.a.34071
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发表时间：
2011-07-01
影响因子：
2
通讯作者：
Ala-Kokko, Leena
中科院分区：
文献类型：
--
作者：
Baker, Stuart;Booth, Carol;Ala-Kokko, Leena
斯蒂克勒综合征的特征是眼、耳、骨骼和口面部异常。我们描述了一个常染色体隐性Stickler综合征的家庭。主要临床表现为高度近视、玻璃体视网膜变性、视网膜脱离、听力下降和身材矮小。发现受影响的家族成员在COL 9A 2中具有纯合的功能丧失突变，c.843_c.846+ 4del 8。一个常染色体隐性Stickler综合征的家庭先前被描述，并发现有一个纯合的功能丧失突变的COL 9A 1。COL 9A 1、COL 9A 2和COL 9A 3编码胶原蛋白IX。所有三种胶原IX α链α 1、α 2和α 3是形成功能性胶原IX分子所需的。在狗中，两个致病基因座已被确定为常染色体隐性眼骨骼发育不良。这种发育不良类似于Stickler综合征。最近，发现COL 9A 2和COL 9A 3中的纯合功能丧失突变与基因座共分离。本研究和以前的研究数据表明，任何胶原IX基因的功能缺失突变均可引起常染色体隐性Stickler综合征。(C)2011 Wiley-Liss，Inc.
Stickler syndrome is characterized by ocular, auditory, skeletal, and orofacial abnormalities. We describe a family with autosomal recessive Stickler syndrome. The main clinical findings consisted of high myopia, vitreoretinal degeneration, retinal detachment, hearing loss, and short stature. Affected family members were found to have a homozygous loss-of-function mutation in COL9A2, c.843_c.846+4del8. A family with autosomal recessive Stickler syndrome was previously described and found to have a homozygous loss-of-function mutation in COL9A1. COL9A1, COL9A2, and COL9A3 code for collagen IX. All three collagen IX a chains, alpha 1, alpha 2, and alpha 3, are needed for formation of functional collagen IX molecule. In dogs, two causative loci have been identified in autosomal recessive oculoskeletal dysplasia. This dysplasia resembles Stickler syndrome. Recently, homozygous loss-of-function mutations in COL9A2 and COL9A3 were found to co-segregate with the loci. Together the data from the present study and the previous studies suggest that loss-of-function mutations in any of the collagen IX genes can cause autosomal recessive Stickler syndrome. (C) 2011 Wiley-Liss, Inc.