Syndromic congenital sensorineural deafness, microtia and microdontia resulting from a novel homoallelic mutation in fibroblast growth factor 3 (FGF3)
Syndromic congenital sensorineural deafness, microtia and microdontia resulting from a novel homoallelic mutation in fibroblast growth factor 3 (FGF3)
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DOI：
10.1038/ejhg.2008.141
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发表时间：
2009-01-01
影响因子：
5.2
通讯作者：
Al-Sayed, MoeenAldeen
中科院分区：
文献类型：
--
作者：
Alsmadi, Osama;Meyer, Brian F.;Al-Sayed, MoeenAldeen
我们在一个沙特大血缘家族的21名患者中发现了成纤维细胞生长因子3(FGF3)的纯合错义突变(C.196G->；T)，该家系表现为常染色体隐性遗传性先天性感音神经性耳聋、小耳和小牙畸形。所有受影响的家庭成员都是共同祖先的后代，他们六代人前生活在一个地理上与世隔绝的小村庄里。这是第二份关于FGF3参与人类综合征性耳聋的报告，独立地证实了该基因在内耳发育中的积极作用。C.196G->；T突变导致66位氨基酸(p.G66C)的甘氨酸被半胱氨酸取代。这种残基在几个物种和18个fgf家族成员中都是保守的。保守的甘氨酸/脯氨酸残基是成纤维细胞生长因子家族蛋白质二级结构‘β-三叶折叠’的中心，这些残基的替换可能会破坏结构，从而影响功能。
We identified a homozygous missense mutation (c.196G -> T) in fibroblast growth factor 3 (FGF3) in 21 affected individuals from a large extended consanguineous Saudi family, phenotypically characterized by autosomal recessive syndromic congenital sensorineural deafness, microtia and microdontia. All affected family members are descendents of a common ancestor who had lived six generations ago in a geographically isolated small village. This is the second report of FGF3 involvement in syndromic deafness in humans, and independently confirms the gene's positive role in inner ear development. The c. 196G -> T mutation results in substitution of glycine by cysteine at amino acid 66 (p.G66C). This residue is conserved in several species and across 18 FGF family members. Conserved glycine/proline residues are central to the 'beta-trefoil fold' characteristic of the secondary structure of FGF family proteins and substitution of these residues is likely to disrupt structure and consequently function.