一个中国先天性并指I-c型家系的致病基因突变的鉴定
Identification of a mutation in causative gene in a Chinese pedigree with congenital syndactyly type I-c
[目的] 应用外显子组测序鉴定一个中国汉族先天性并指I-c型家系的致病基因突变。[方法] 提取该家系成员的外周血DNA，应用外显子组测序技术，对家系典型先证者(IV:1)进行高通量测序，并通过公共数据库(dbSNP137、 千人基因组计划、HapMap、和YH数据库)及华大基因内部数据库筛查候选变异及同义突变。使用Sanger测序法进行家系内疾病共分离分析，并在100例正常对照人群中进行突变验证。[结果] 通过对该家系先证者(IV:1)进行外显子组测序，共得到106958个基因变异，其中14830为非同义替换。所有变异经四个公共数据库及华大基因内部数据库过滤，生物信息学分析后，获得候选变异HOXD13基因c.917G>A (p.R306Q)突变。家系内其他成员Sanger测序后发现该突变在家系中发生疾病共分离。在100例无血缘关系的同种族正常对照样本中，Sanger测序没有发现该突变。[结论] 利用外显子组测序技术，我们鉴定出HOXD13基因c.917G>A (p.R306Q)突变是该中国汉族先天性并指I-c型家系的致病基因突变。
基础医学遗传学
遗传学并指外显子组测序HOXD13基因突变
林琼芬,朱安定,邓昊,肖晶晶,管李萍,贺全勇,谭婷,虢毅,宋治,杨志坚.一个中国先天性并指I-c型家系的致病基因突变的鉴定[EB/OL].(2016-01-06)[2025-10-25].http://www.paper.edu.cn/releasepaper/content/201601-112.点此复制
Objective: The aim of this study was to identify the causative gene mutation in a Chinese Han pedigree with congenital syndactyly I-c by exome sequencing. Methods: Genomic DNA of members in this family was extracted from peripheral blood. Exome sequencing was conducted on the proband (IV:1) after DNA extraction. All candidate variants and synonymous substitutions were filtered against the dbSNP137, 1000 genomes project, HapMap, YanHuang (YH), and exome sequencing data from BGI-shenzhen. Sanger sequencing was employed to verify the identified potential disease-causing variant in other members and 100 unrelated ethnically matched normal controls. Results: After exome sequencing of the proband, 106958 genetic variants, including 14830 nonsynonymous variants were generated. We excluded known variants identified in dbSNP137, 1000 genomes project, HapMap, YH database, and exome sequencing data from BGI-shenzhen. A missense mutation, c.917G>A (p.R306Q) was identified in the HOXD13 gene. Sanger sequencing verified this mutation in all affected members, while was absent in unaffected members and 100 ethnically matched normal controls. Conclusions: We identified a missense mutation c.917G>A (p.R306Q) in the HOXD13 gene by exome sequencing, which may be responsible for syndactyly type I-c in this family.
GeneticsSyndactylyExome sequencingHOXD13 geneMutation
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