CAJ | 학술논문

目的明确一个具有常染色体显性遗传特点的珊瑚状先天性白内障家系中致病基因及其突变的类型.方法系列病例研究.对珊瑚状遗传性先天性白内障一家系共18名成员进行详细的临床检查,确定其临床表型.提取9位家系成员(4名患者,均为男性,3名正常同胞,2名配偶,年龄4～79岁)的外周血DNA,利用连锁分析进行排除定位,确定候选基因.对连锁区域内的候选基因进行基因序列分析.结果连锁分析结果显示在D2S325得到最高LOD值为1.51,在D11S925得到LOD值为1.20,支持其与该家系先天性白内障疾病相关候选基因有连锁关系；CRYGD、CRYGC、CRYAB基因可能为该家系先天性白内障疾病相关候选基因.测序结果显示该家系患者CR YGD基因第二外显子第70位碱基由C突变为A,导致第23位的脯氨酸变成了苏氨酸(P23T),且这一错义突变与疾病表型完全共分离.CRYGC基因、CRYAB基因编码区未发现突变.结论珊瑚状遗传性先天性白内障一家系的致病原因是CRYGD基因,第二外显子第70位碱基由C突变为A.
목적 명학일개구유상염색체현성유전특점적산호상선천성백내장가계중치병기인급기돌변적류형.방법 계렬병례연구.대산호상유전성선천성백내장일가계공18명성원진행상세적림상검사,학정기림상표형.제취9위가계성원(4명환자,균위남성,3명정상동포,2명배우,년령4～79세)적외주혈DNA,이용련쇄분석진행배제정위,학정후선기인.대련쇄구역내적후선기인진행기인서렬분석.결과 련쇄분석결과현시재D2S325득도최고LOD치위1.51,재D11S925득도LOD치위1.20,지지기여해가계선천성백내장질병상관후선기인유련쇄관계；CRYGD、CRYGC、CRYAB기인가능위해가계선천성백내장질병상관후선기인.측서결과현시해가계환자CR YGD기인제이외현자제70위감기유C돌변위A,도치제23위적포안산변성료소안산(P23T),차저일착의돌변여질병표형완전공분리.CRYGC기인、CRYAB기인편마구미발현돌변.결론 산호상유전성선천성백내장일가계적치병원인시CRYGD기인,제이외현자제70위감기유C돌변위A.
Objective To map and to identify the causal gene of autosomal dominant congenital coralliform cataract ( ADCC ) in a Chinese family. Methods Case series study.Clinical features of all affected members in this family were examined. Blood samples were collected from nine family members for genetic linkage analysis.Polymorphic microsatellite markers were selected from the regions which harbor all known loci linked with ADCC. Direct genomic sequencing was used to evaluate the candidate gene.Results The affected members in this family showed classic phenotype of ADCC. The maximum two-point LOD score of 1.51 was obtained for marker D2S325 (θ =0).The LOD score of 1.20 was obtained for marker D11S925.The CRYGC/CRYGD gene located on 2q33-q35 and the CRYAB gene located on 11q22-q22.3.Therefore,the CRYGC/CRYGD and CRYAB gene may be the candidate gene in this family.Sequencing of the coding regions of the CRYGD gene showed the presence of a heterozygous C→A transversion at nucleotide 70 in exon 2 of CRYGD that is associated with cataracts in this family.This mutation resulted in a proline to threonine substitution at amino acid 23 of the protein in the first of the four Greek key motifs that characterized this protein. No mutation in all exons of CRYGC and CRYAB gene were found in the family.Conclusion Direct DNA sequence analysis revealed a C-to-A transition at nucleotide 70 of the CRYGD gene in this ADCC family