CAJ | 학술논문

目的：对一个来自浙江省杭州地区的三代先天性白内障家系进行常染色体显性遗传基因的突变分析，以寻找其可能的致病基因及突变位点。方法该家系共10例成员，其中包括4例患者。10例家系成员在浙江省人民医院眼科中心接受眼科专科检查及全身检查，以排除存在白内障以外的眼部及全身疾患。10例家系成员各抽取外周血5ml，提取基因组DNA。针对国内外文献报道的与常染色体显性遗传先天性白内障相关的18个基因（CRYAA、CRYAB、CRYBA1、CRYBA2、CRYBA4、CRYBB1、CRYBB2、CRYGC、CRYGD、CRYGS、GJA3、GJA8、MIP、BFSP、HSF4、PITX3、EPHA2、PAX6）设计引物，进行PCR扩增，对扩增产物进行测序和序列分析，了解这10例家系成员的以上基因是否存在相应的序列。结果临床眼科检查显示该家系先天性白内障类型为粉尘状白内障。候选基因序列测定显示在CRYAA第1个外显子中第6位碱基发生C→T置换，氨基酸同为天门冬氨酸。该家系中所有患者均有此改变，而所有的正常家系成员均无此改变。结论 CRYAA第1个外显子中第6位碱基发生C→T的同义突变可能是导致该家系先天性白内障发生的致病原因。
목적：대일개래자절강성항주지구적삼대선천성백내장가계진행상염색체현성유전기인적돌변분석，이심조기가능적치병기인급돌변위점。방법해가계공10례성원，기중포괄4례환자。10례가계성원재절강성인민의원안과중심접수안과전과검사급전신검사，이배제존재백내장이외적안부급전신질환。10례가계성원각추취외주혈5ml，제취기인조DNA。침대국내외문헌보도적여상염색체현성유전선천성백내장상관적18개기인（CRYAA、CRYAB、CRYBA1、CRYBA2、CRYBA4、CRYBB1、CRYBB2、CRYGC、CRYGD、CRYGS、GJA3、GJA8、MIP、BFSP、HSF4、PITX3、EPHA2、PAX6）설계인물，진행PCR확증，대확증산물진행측서화서렬분석，료해저10례가계성원적이상기인시부존재상응적서렬。결과림상안과검사현시해가계선천성백내장류형위분진상백내장。후선기인서렬측정현시재CRYAA제1개외현자중제6위감기발생C→T치환，안기산동위천문동안산。해가계중소유환자균유차개변，이소유적정상가계성원균무차개변。결론 CRYAA제1개외현자중제6위감기발생C→T적동의돌변가능시도치해가계선천성백내장발생적치병원인。
Objective To identify the pathogenic gene of congenital cataract in a Chinese family. Methods In a three- generation Chinese family 4 members were affected by congenital cataract in both eyes. Ten individuals from this family underwent ophthalmologic and physical examination in Zhejiang Provincial People's Hospital. The DNA was extracted from pe-riphery blood samples and amplified by PCR. The PCR products were sequenced and analyzed to detect mutations of 18 autoso-mal dominant congenital contact- related genes (CRYAA, CRYAB, CRYBA1, CRYBA2, CRYBA4, CRYBB1, CRYBB2, CRYGC, CRYGD, CRYGS, GJA3, GJA8, MIP, BFSP, HSF4, PITX3, EPHA2 and PAX6). Results The congenital cataract in this family is pulverulent type. A C→T mutation at 6 base in the first exon of CRYAA gene was detected, which was coding the same amino acid (asparaginic acid). Al the patients in this family had this mutation, while the mutation was not detected in normal family mem-bers. Conclusion The study identifies a mutation in CRYAA, which may contribute to the pathogenesis of congenital cataract in this family.