Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes
Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/Stickler phenotypes
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DOI：
10.1086/302585
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发表时间：
1999-10-01
影响因子：
9.8
通讯作者：
Ala-Kokko, L
中科院分区：
文献类型：
--
作者：
Annunen, S;Körkkö, J;Ala-Kokko, L
Stickler和马歇尔综合征是一种显性遗传性软骨发育不良，其特征为面中部发育不全、高度近视和感觉神经性听力缺陷。由于这些综合征的特征重叠，人们一直在争论它们是否是单一综合征的不同表现的不同实体。在COL 2A 1基因中发现了几种引起Stickler综合征的突变，在COL 11 A1基因中检测到一种引起Stickler综合征的突变和一种引起马歇尔综合征的突变。我们在这里的特征的COL 11 A1基因的基因组结构。对Stickler、Stickler样或马歇尔综合征患者的筛查发现了23种新的突变。基因型-表型比较显示马歇尔综合征表型与COL 11 A1基因C-末端区域54-bp外显子剪接突变相关。COL 2A 1中的零等位基因突变。该基因导致Stickler综合征的典型表型。然而，一些患者同时表现出马歇尔和Stickler综合征的表型。
Stickler and Marshall syndromes are dominantly inherited chondrodysplasias characterized by midfacial hypoplasia, high myopia, and sensorineural-hearing deficit. Since the characteristics of these syndromes overlap, it has been argued whether they are distinct entities of different manifestations of a single syndrome. Several mutations causing Stickler syndrome have been found in the COL2A1 gene, and one mutation causing Stickler syndrome and one causing Marshall syndrome have been detected in the COL11A1 gene. We characterize here the genomic structure of the COL11A1 gene. Screening of patients with Stickler, Stickler-like, or Marshall syndrome pointed to 23 novel mutations. Genotypic-phenotypic comparison revealed an association between the Marshall syndrome phenotype and splicing mutations of 54-bp exons in the C-terminal region of the COL11A1 gene. Null-allele mutations in the COL2A1. gene led to a typical phenotype of Stickler syndrome. Some patients, however, presented with phenotypes of both Marshall and Stickler syndromes.