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目的分析国人6个常染色体显性先天性白内障(ADCC)家系的基因突变,确定其致病基因及突变形式。设计实验性研究。研究对象6个ADCC家系。方法应用聚合酶链反应(PCR)和DNA直接测序方法,对家系进行ADCC常见致病基因突变分析。主要指标基因序列。结果对12个ADCC常见致病基因(CRYAA,CRYAB,CRYBB1,CRYBB2,CRYBA1,CRYGS,CRYGC,CRYG D,GJA8,GJA3,MIP,BFSP2)外显子及外显子内含子连接区进行DNA直接测序,发现7种碱基序列改变,并导致相应编码氨基酸变化,分别是位于CRYBB2基因cDNA序列445位C->T(R145W),452位A->(Q147R),461位C->T(T150M)和388位G->T碱基改变(D126Y);GJa8基因cDNA序列1055位A->G碱基替代(E352G);BFSP2基因cDNA序列1295位C-> A(A407D)及MIP基因cDNA序列96位T->A碱基改变(Y23N)。其中前3种序列改变已报道为单核苷酸多态性(SNP),经过对相应家系其他成员的分析发现后4种序列改变也为SNP。结论先天性白内障的临床表型与基因型均有明显的遗传异质性,本试验在12个基因外显子及外显子内含子连接区内未发现导致这6个ADCC家系疾病表型的致病基因突变,但是发现了7种SNP改变,其中4种为本研究首次发现。
Objective To analyze the genetic mutations in 6 Chinese families with autosomal dominant congenital cataract (ADCC) and determine their causative genes and their mutated forms. Design experimental research. Study object 6 ADCC family. Methods Polymerase chain reaction (PCR) and DNA direct sequencing were used to analyze the prevalence of common pathogenic mutations in ADCC. The main indicator gene sequence. Results The direct and indirect exon intron regions of 12 ADCC genes (CRYAA, CRYAB, CRYBB1, CRYBB2, CRYBA1, CRYGS, CRYGC, CRYG D, GJA8, GJA3, MIP and BFSP2) Sequencing and found seven kinds of base sequence changes, and lead to the corresponding encoded amino acid changes, respectively, located in the CRYBB2 cDNA sequence 445 C-> T (R145W), 452 A -> (Q147R), 461 C-> T T150M) and 388 G → T base changes (D126Y); GJa8 cDNA sequence 1055 A-> G base substitution (E352G); BFSP2 cDNA sequence 1295 C-> A (A407D) and MIP cDNA Sequence 96 T-> A base change (Y23N). The first three changes have been reported as single nucleotide polymorphisms (SNPs). After analysis of the other members of the corresponding pedigree, four of the sequence changes were also SNPs. Conclusions The clinical phenotype and genotype of congenital cataract have obvious genetic heterogeneity. In the present study, no phenotypes were found in the 12 ADCC families and exon intron junctions Seven mutations were found, of which four were found for the first time in this study.