Gu Feng, Li Rong, Ma Xi Xin, Shi Li Song, Huang Shang Zhi, Ma Xu
Department of Genetics, National Research Institute for Family Planning, Beijing, China.
Mol Vis. 2006 Jan 10;12:26-31.
To identify the genetic defect in autosomal dominant congenital cataracts in a six generation Chinese family.
Clinical and ophthalmological examinations were performed on the affected and unaffected family members. All the members were genotyped with microsatellite markers at loci which were considered to be associated with cataracts. A two-point LOD score was calculated using the Linkage package after genotyping. A mutation was detected by direct sequencing using gene specific primers.
Clinical heterogeneity was observed within this family, three affected individuals showed nuclear cataract and others had coralliform cataracts. Significant evidence of linkage was obtained at markers D2S325 (LOD score [Z]=3.10, recombination fraction [theta]=0.0) and D2S1782 (Z=5.97, theta=0.0), respectively. Haplotype analysis indicated that the cataract gene was close to those two markers. Sequencing of the gammaD-crystallin gene (CRYGD) revealed a C>T transition in exon 2, that causes a conservative substitution of Arg to Cys at codon 14 (R14C). This mutation co-segregated with all affected individuals and was not observed in unaffected or 100 normal unrelated individuals. Bioinformatic analyses also showed that a highly conserved region was located at Arg14.
This study is the first reported case with phenotype of coralliform/nuclear cataract that associated with the mutation of Arg14Cys (R14C) CRYGD.
在一个六代中国家系中鉴定常染色体显性遗传性先天性白内障的基因缺陷。
对家系中患病和未患病成员进行临床及眼科检查。使用被认为与白内障相关位点的微卫星标记对所有成员进行基因分型。基因分型后，使用Linkage软件包计算两点连锁分析LOD值。通过基因特异性引物直接测序检测突变。
该家系中观察到临床异质性，三名患者表现为核性白内障，其他患者为珊瑚状白内障。分别在标记D2S325（LOD值[Z]=3.10，重组率[θ]=0.0）和D2S1782（Z=5.97，θ=0.0）处获得显著的连锁证据。单倍型分析表明白内障基因与这两个标记紧密连锁。γD-晶状体蛋白基因（CRYGD）测序显示外显子2中有一个C>T转换，导致第14密码子处的精氨酸保守替换为半胱氨酸（R14C）。该突变与所有患病个体共分离，在未患病个体或100名正常无关个体中未观察到。生物信息学分析还表明，高度保守区域位于精氨酸14处。
本研究首次报道了与CRYGD基因的Arg14Cys（R14C）突变相关的珊瑚状/核性白内障表型病例。
