Identification a novel MYOC gene mutation in a Chinese family with juvenile-onset open angle glaucoma
Identification a novel MYOC gene mutation in a Chinese family with juvenile-onset open angle glaucoma
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发表时间：
2010-08
期刊：
影响因子：
2.2
通讯作者：
Xin Zhao;Chao-Shan Yang;Y. Tong;Xiao-hui Zhang;Liang Xu;Yang Li-
中科院分区：
文献类型：
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作者：
Xin Zhao;Chao-Shan Yang;Y. Tong;Xiao-hui Zhang;Liang Xu;Yang Li-
目的描述一个青少年型开角型青光眼（JOAG）家系的临床和遗传学特征。方法对1个家系进行临床检查并随访5年。在获得知情同意后，从所有参与者的静脉血中提取基因组DNA。利用MYOC基因周围的3个微卫星标记（D1 S196、D1 S2815和D1 S218）对该家系进行连锁分析。通过PCR扩增DNA片段直接测序和限制性片段长度多态性（RFLP）分析，对MYOC所有编码外显子进行突变筛查。通过Garnier-Osguthorpe-Robson（戈尔）方法进行的生物信息学分析预测了检测到的变体对MYOC蛋白二级结构的影响。结果经临床检查和家系分析，发现一个三代家系，其中7名成员诊断为JOAG，3名成员诊断为高眼压症，5名成员为正常人。通过基因分型，该家系显示与染色体1 q24 -25上的MYOC连锁。该家系MYOC基因突变筛查结果显示，在cDNA序列的第1348位（p.N450Y）有一个A→T的转换。这种错义突变与该家系的疾病表型共分离，但在100名正常对照中未发现。通过戈尔方法对p.N450 Y的二级结构预测揭示了在氨基酸447处用β折叠替换卷曲。结论早发性JOAG伴不完全显性遗传，与MYOC的一种新突变一致。这一发现为该家族成员提供了症状前分子诊断，并有助于进一步的遗传咨询。
Purpose To describe the clinical and genetic findings in one Chinese family with juvenile-onset open angle glaucoma (JOAG). Methods One family was examined clinically and a follow-up took place 5 years later. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Linkage analysis was performed with three microsatellite markers around the MYOC gene (D1S196, D1S2815, and D1S218) in the family. Mutation screening of all coding exons of MYOC was performed by direct sequencing of PCR-amplified DNA fragments and restriction fragment length polymorphism (RFLP) analysis. Bioinformatics analysis by the Garnier-Osguthorpe-Robson (GOR) method predicted the effects of variants detected on secondary structures of the MYOC protein. Results Clinical examination and pedigree analysis revealed a three- generation family with seven members diagnosed with JOAG, three with ocular hypertension, and five normal individuals. Through genotyping, the pedigree showed a linkage to the MYOC on chromosome 1q24–25. Mutation screening of MYOC in this family revealed an A→T transition at position 1348 (p. N450Y) of the cDNA sequence. This missense mutation co-segregated with the disease phenotype of the family, but was not found in 100 normal controls. Secondary structure prediction of the p.N450Y by the GOR method revealed the replacement of a coil with a β sheet at the amino acid 447. Conclusions Early onset JOAG, with incomplete penetrance, is consistent with a novel mutation in MYOC. The finding provides pre-symptomatic molecular diagnosis for the members of this family and is useful for further genetic consultation.