河南汉族一个成骨不全家系的COL1A1基因突变检测  

Analysis of COL1A1 gene mutation in an ethnic Han Chinese family from Henan affected with osteogenesis imperfecta

作　　者：黄艳梅[1] 郭利伟[1] 王东浩[1] 杨明娟[1] 杨保胜[2] 

机构地区：[1]新乡医学院法医物证学教研室,河南453003 [2]新乡医学院基础医学院,河南453003

出　　处：《中华医学遗传学杂志》2016年第5期653-656,共4页Chinese Journal of Medical Genetics

基　　金：新乡医学院高学历人才启动基金资助项目（No.2005）;河南省教育科学“十二五”规划重点课题（2013-JKGHB-0035）

摘　　要：目的对河南汉族一个成骨不全家系的COL1A1基因进行分析，寻找其致病突变位点。方法采用PCR和DNA直接测序法分析该家系患者COL1A1基因所有的外显子及内含子序列，并与该家系的正常个体、50名健康个体及GenBank的序列进行比较。结果该家系COL1A1基因共发现15个突变位点，包括1个错义突变、1个同义突变及13个内含子变异。所有患者均检出COL1A1基因第50外显子的杂合性错义突变c．4193T〉G，该突变导致P．11398S（异亮氨酸变为丝氨酸），先证者的父亲也存在此突变但表型正常，在家系的其他健康成员及50名健康对照者中则未发现该突变。结论该家系的成骨不全疾病类型可能为与COL1A1基因相关的常染色体显性遗传伴外显不全或常染色体隐性遗传。Objective To identify potential mutation of COL1A1 gene in an ethnic Han Chinese family from Henan affected with osteogenesis imperfecta （OI）. Methods Peripheral blood samples were collected from all 11 members of the family and 50 healthy adults for the extraction of genomic DNA. All exons and introns of the COL1A1 gene were amplified by polymerase chain reaction and subjected to direct sequencing. Mutations found in the proband were analyzed through comparison with other members of the family, 50 healthy individuals and sequence from the GenBank. Results Fifteen sequence variants were discovered, which included 1 missense mutation, 1 synonymous mutation and 13 intronic mutations. All of the 4 patients from the family were detected as having carried a novel heterozygous missense mutation （c. 4193T〉G, p. I1398S） in exon 50 of the COL1A1 gene. The father of the proband has carried the same mutation but had a normal phenotype. The same mutation was not found in other healthy members of the family. Conclusion The OI type of this family may have been autosomal dominant with incomplete penetrance or autosomal recessive associated with COL1A1 gene mutations.

关 键 词：成骨不全 COL1A1基因 突变 外显不全 常染色体隐性遗传 

分 类 号：R681.1[医药卫生—骨科学]