Transcription factor HAND2 mutations in sporadic Chinese patients with congenital heart disease
Transcription factor HAND2 mutations in sporadic Chinese patients with congenital heart disease
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DOI：
10.3760/cma.j.issn.0366-6999.2010.13.002
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发表时间：
2010-07-05
影响因子：
6.1
通讯作者：
Li Zhong-zhi
中科院分区：
文献类型：
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作者：
Shen Lei;Li Xiao-feng;Li Zhong-zhi
背景：碱性螺旋-环-螺旋转录因子HAND 2在心脏形态发生中起重要作用。然而，HAND 2基因突变在先天性心脏病（CHD）中的发生率以及HAND 2基因型与CHD表型之间的相关性尚未得到广泛研究。方法我们扩增了131例诊断为先天性右心室、流出道、结果7例突变，其中3例为错义突变12例患者的非翻译区有3个突变（241 A>G、604 C>T和3237 T>A），1个等位基因突变（H14 H）。两个非同源突变均位于N-末端的转录激活结构域中。在250例正常人中仅发现一个突变（S36 N）。结论HAND 2可能是右室流出道狭窄的一个潜在候选基因。对有HAND 2突变家族史的人进行进一步研究将有助于令人信服地将他们的基因型与CHD的发病机制联系起来。中华医学杂志2010;123（13）：1623-1627
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 HAND2 gene 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. Chin Med J 2010;123(13):1623-1627