Transcription factor HAND2 mutations in sporadic Chinese patients with congenital heart disease  

作　　者：SHEN Lei LI Xiao-feng SHEN A-dong WANG Qiang LIU Cai-xia GUO Ya-jie SONG Zhen-jiang LI Zhong-zhi 

机构地区：[1]Cardiac Centre Beijing Children's Hospital affiliated to Capital Medical University, Beijing 100045, China [2]Department of Orthopaedics, Beijing Hospital, Beijing 100730,China

出　　处：《Chinese Medical Journal》2010年第13期1623-1627,共5页中华医学杂志（英文版）

基　　金：This work was supported by a grant from the National Natural Science Foundation of China （No. 30672193）.Acknowledgements： We are grateful to the patients and their families for the cooperation, to the members of the Paediatric Heart Centre for support and staff of the Central Laboratory of Molecular Biology for the technical assistance. We specially thank Dr. ZHU Xiao-quan for the excellent advice and assistance and Dr. ZHANG Wei-min for helpful patient information.

摘　　要：Background The basic helix-loop-helix transcription factor HAND2 plays an essential role in cardiac morphogenesis. However, the prevalence of HAND2 mutations in congenial heart disease （CHD） and the correlation between the HAND2 genotype and CHD phenotype have not been studied extensively. Methods We amplified the exons and the flanking intron sequences of the HAND2gene in 131 patients diagnosed with congenital defects of the right ventricle, outflow tract, aortic artery or cardiac cushion and confirmed the mutations by sequencing. Results Seven mutations including three missense mutations （P11R, S36N and V83L）, one isonymous mutation （H14H） and three mutations in untranslated region （241A〉G, 604C〉T and 3237T〉A） were identified in 12 out of the 131 patients. Both nonisonymous mutations are located in the transcriptional activation domain on the N-terminus. Only one mutation （S36N） was identified in 250 normal healthy controls. The distribution of 3637T〉A is the unique one which was different between the 2 groups. Conclusions HAND2 may be a potential candidate gene of stenosis of the right ventricle, outflow tract. Further study of those with a family history of HAND2 mutations will help convincingly relate their genotype to the pathogenesis of CHD.Background The basic helix-loop-helix transcription factor HAND2 plays an essential role in cardiac morphogenesis. However, the prevalence of HAND2 mutations in congenial heart disease （CHD） and the correlation between the HAND2 genotype and CHD phenotype have not been studied extensively. Methods We amplified the exons and the flanking intron sequences of the HAND2gene in 131 patients diagnosed with congenital defects of the right ventricle, outflow tract, aortic artery or cardiac cushion and confirmed the mutations by sequencing. Results Seven mutations including three missense mutations （P11R, S36N and V83L）, one isonymous mutation （H14H） and three mutations in untranslated region （241A〉G, 604C〉T and 3237T〉A） were identified in 12 out of the 131 patients. Both nonisonymous mutations are located in the transcriptional activation domain on the N-terminus. Only one mutation （S36N） was identified in 250 normal healthy controls. The distribution of 3637T〉A is the unique one which was different between the 2 groups. Conclusions HAND2 may be a potential candidate gene of stenosis of the right ventricle, outflow tract. Further study of those with a family history of HAND2 mutations will help convincingly relate their genotype to the pathogenesis of CHD.

关 键 词：BHLH HAND2 congenital heart disease transcription factor MUTATION 

分 类 号：Q754[生物学—分子生物学] R541.1[医药卫生—心血管疾病]