诊断学理论与实践2013，Vol.12Issue(1)：32-37,6.DOI:10.3969/j.issn.1671-2870.2013.01.008
腓骨肌萎缩症2型大家系的基因定位及分子诊断
Gene localization and molecular diagnosis in a large pedigree of Chareot-Marie-Tooth Disease type 2
摘要
Abstract
Objective To study the clinical and genetic characteristics of Chareot-Marie-Tooth Disease type 2 (CMT2) in a large pedigree, and to localize and clone the disease gene of the pedigree for molecular diagnosis. Methods The pedigree came from Shandong Province, DNA sample and clinical data were obtained and pedigree analysis was performed to analyze the genetic characteristics of CMT2. A genome-wide screening was performed by using 401 microsatellite markers from the ABI Prism Linkage Mapping Set Version 2.5. MLINK program from LINKAGE 5.1 computer program package was used for two-point linkage analysis. The exons and exon-intron boundaries of 20 candidate genes were amplified and sequenced. The resulting sequences were analyzed using Chromosome program. Results The pedigree is consistent with pattern of the autosomal dominant inheritance. A tightly linked locus at 10pl4 was found in this pedigree. DNA sequencing in 20 candidate genes revealed a nonsense mutation C.1455T>G (p.Tyr485*) in exon 8 of dehydrogenase El and transketolase domain containing 1 (DHTKD1) in all 8 patients, but not in other unaffected individuals in this family and 250 unrelated normal persons. Conclusions The above-mentioned data indicates that the nonsense mutation of DHTKD1 may contribute to the pathogenesis of CMT2.关键词
腓骨肌萎缩症2型/基因组扫描/基因定位/脱氢酶E1和转酮酶结构域1/分子诊断Key words
Chareot-Marie-Tooth Disease type 2/ Genome-wide scan/ Gene localization/ Dehydrogenase El and transketolase domain containing 1 (DHTKD1)/ Molecular diagnosis分类
医药卫生引用本文复制引用
郭文婷,孙莲花,徐汪洋,马建芳,陈生弟,冀保军,孙福廷,袁文涛,黄薇..腓骨肌萎缩症2型大家系的基因定位及分子诊断[J].诊断学理论与实践,2013,12(1):32-37,6.基金项目
国家自然科学基金(31071107) （31071107）
