遗传性先天性核性白内障家系CRYAB错义突变  

CRYAB missense mutation in a family with congenital nuclear cataract

作　　者：郑玲[1] 金怡轩 谷静芝[1] 

机构地区：[1]哈尔滨医科大学附属第二医院眼科,黑龙江省哈尔滨市150086 [2]佛山市南海区人民医院,广东省佛山市528200

出　　处：《眼科新进展》2012年第8期712-715,共4页Recent Advances in Ophthalmology

基　　金：哈尔滨科技创新人才专项基金(编号:2006RFQXS087)~~

摘　　要：目的鉴定一个四代常染色体显性遗传性先天性白内障(autosomal dominantcongenital cataract,ADCC)家系的致病基因。方法收集ADCC一家系资料,全面检查,提取血液DNA,在已报道的与先天性白内障相关的致病基因和其附近选择合适的微卫星标记位点进行连锁分析,对提示连锁的染色体区域内的已知候选基因测序。结果系谱图分析示该ADCC家系符合常染色体显性遗传特点。裂隙灯显微镜检查示全部患者表型均为核性。连锁分析示致病基因定位在11q22.3-23.1区域内,对此区域内的候选基因B-晶状体蛋白基因进行测序,发现其外显子1第58位核苷酸C→T错义突变,引起所编码的第20位脯氨酸被丝氨酸取代(P20S)。结论 B-晶状体蛋白的点突变导致了该家系遗传性先天性核性白内障,丰富了基因型-表型谱,并为分子机制的研究提供了新线索。Objective To identify the virulence gene in a four-generation Chinese family with autosomal dominant congenital cataract（ADCC）.Methods A four-generation Chinese family with ADCC was recruited.Detail examination was made,and the genomic DNA was extracted.Microsatellite markers close proximity to genes and loci previously reported involving in human congenital cataract was chosen.Linkage analysis was performed for location analysis.Candidate gene sequencing was performed to screen out the disease-causing mutation.Results The pedigree chart analysis showed that this family was consistent with heredity characterizes of autosomal dominant inheritance.Slit lamp examination showed the phenotype of the family was nuclear cataract.The disease gene was mapped to chromosome 11 in region q22.3-23.1.Sequencing of the coding regions of B-crystallin showed the presence of a heterozygous C→T transversion at nucleotide 58 in exon 1,which caused that the proline was replaced by serine（P20S）.Conclusion Point mutation in B-crystallin causes the ADCC of the family,which expands the genotypic-phenotypic spectrum of ADCC and offers a new clue to explore the molecular mechanism.

关 键 词：先天性核性白内障 基因突变 遗传 

分 类 号：R774.1[医药卫生—眼科]