Fibrochondrogenesis Results from Mutations in the COL11A1 Type XI Collagen Gene
Fibrochondrogenesis Results from Mutations in the COL11A1 Type XI Collagen Gene
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DOI：
10.1016/j.ajhg.2010.10.009
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发表时间：
2010-11-12
影响因子：
9.8
通讯作者：
Cohn, Daniel H.
中科院分区：
文献类型：
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作者：
Tompson, Stuart W.;Bacino, Carlos A.;Cohn, Daniel H.
纤维软骨生成是一种严重的常染色体隐性短肢骨骼发育不良。在纤维软骨生成的单个病例中，全基因组SNP基因分型通过检测三个纯合子区域来确定未知的祖先血统因为表型的主要骨骼性质。通过UCLA基因表达工具将389个基因定位于纯合子区间，通过它们的表达与已知的软骨选择基因的相关性，优先进行突变分析，UGET编码XI型胶原α1链的基因(COL11A1)是COL11A1三个候选区间中唯一的软骨选择基因。在两个遗传独立的纤维软骨形成病例中，序列分析表明，每个COL11A1是一个复合杂合子，导致一个等位基因的功能丧失，另一个突变预示着保守的三螺旋甘氨酸残基的替代。错义突变携带者的父母都有近视性早期听力损失，提示COL11A1是轻度、显性遗传性听力损失的基因座。这些发现确认COL11A1是纤维软骨形成的基因座，并提示在纤维软骨形成中可能存在表型表现。
Fibrochondrogenesis is a severe, autosomal recessive, short limbed skeletal dysplasia In a single case of fibrochondrogenesis, whole genome SNP genotyping identified unknown ancestral consanguinity by detecting three autozygous regions Because of the predominantly skeletal nature of the phenotype the 389 genes localized to the autozygous intervals were prioritized for mutation analysis by correlation of their expression with known cartilage selective genes via the UCLA Gene Expression Tool, UGET The gene encoding the alpha 1 chain of type XI collagen (COL11A1) was the only cartilage selective gene among the three candidate intervals Sequence analysis of COL11A1 in two genetically independent fibrochondrogenesis cases demonstrated that each was a compound heterozygote for a loss of function mutation on one allele and a mutation predicting substitution for a conserved triple helical glycine residue on the other The parents who were carriers of missense mutations had myopia Early onset hearing loss was noted in both parents who carried a loss of function allele, suggesting COL11A1 as a locus for mild, dominantly inherited hearing loss These findings identify COL11A1 as a locus for fibrochondrogenesis and indicate that there might be phenotypic manifestations among carriers