先天性白内障一家系晶状体蛋白突变基因筛查

Screen of crystallin protein mutation genes in a hereditary congenital cataract family

目的对先天性白内障一家系进行晶状体蛋白致病基因的初步筛查。方法通过聚合酶链反应(PCR)对先天性白内障一家系中4代8例患者进行CRYAA、CRYAB、CRYA1/A3、CRYBB2、CRYGC和CRYGD6个候选基因的外显子及内含子扩增,扩增产物进行直接测序,测序结果与GeneBank中原始序列进行BLAST比对分析。结果该家系每代均有先天性白内障患者,遗传方式为常染色体显性遗传。该家系的CRYAA、CRYAB、CRYA1/A3、CRYBB2、CRYGC和CRYGD6个晶状体蛋白候选基因的外显子及其邻近的内含子与基因库对照未发现任何突变。结论CRYAA、CRYAB、CRYA1/A3、CRYBB2、CRYGC和CRYGD为该先天性白内障家系的非致病基因。

Background With the development of biological techniques,the study on the pathogenesis of disease-causing genes of congenital cataracts has substantial progress. Some positive results of screen of mutation gene in congenital cataract family has been reported, but the report of negative result is rate. Objective The present study attempts to screen the mutation of CRYAA, CRYAB, CRYA1/A3, CRYBB2, CRYGC and CRYGD gene in a Chinese family with autosomal dominant congenital cataract. Methods The periphery blood samples were exacted from 8 patients of 4 generations of with congenital cataract in this family. The complete coding region and intron spliced sites of CRYAA, CRYAB, CRYA1/A3, CRYBB2, CRYGC and CRYGD were amplified with polymerase chain reaction （PCR） , and the products of PCR were directly sequenced. The control blood samples were from 10 normal subjects. This study followed the Declaration of Helsinki. Written informed eonsent was obtained from all of the patients. Results The patients were found in each generation in this family and the mode of inheritance was in accordance with the characteristic of autosomal dominant inheritance. The sequence of amplified genetic fragments of CRYAA, CRYAB, CRYA1/A3, CRYBB2,CRYGC and CRYGD genes were inaccordance with those of normal subjects and GeneBank. No any mutation loci was found in all of the patients of this family. Conclusion CRYAA, CRYAB, CRYA1/A3, CRYBB2,CRYGC and CRYGD genes is not the causing-disease genes in this family.