摘要
目的:研究一个腓骨肌萎缩症2型(Chareot-Marie-Tooth Disease type2,CMT2)大家系的临床及遗传学特征,定位和克隆该家系的致病基因用于分子诊断。方法:采集山东省一个CMT2大家系,采用家系分析法观察该家系的遗传规律,并采用连锁分析试剂盒(Version 2.5)进行全基因组扫描,用LINKAGE软件(Version 5.1)中的MLINK程序作连锁分析,运用直接测序法对20个候选基因的外显子及外显子-内含子边界区序列进行测序,结果用CHROMOSOME软件进行序列分析。结果:该CMT2家系符合常染色体显性遗传的特征,连锁分析表明位于10p14存在一个致病基因位点,测序分析显示脱氢酶E1和转酮酶结构域1(DHTKD1)的一个无义突变[c.1455T>G(p.Tyr485*)]存在于该家系的所有8个患者中,而不存在于该家系任何未受累者及250名正常对照者中。结论:本研究结果提示DHTKD1的无义突变可能是CMT2发病的分子基础。
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 mierosatellite 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 10p14 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 E1 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.
出处
《诊断学理论与实践》
2013年第1期32-37,共6页
Journal of Diagnostics Concepts & Practice
基金
国家自然科学基金(31071107)
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
Chareot-Marie-Tooth Disease type 2
Genome-wide scan
Gene localization
Dehydrogenase E1 andtransketolns~ dnmnin cnntninin~, 1 ~DHTKD1 ~： Mnl^clJlnr din^nn^i~
