Transcription factor HAND2 mutations in sporadic Chinese patients with congenital heart disease.
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.
Shen
Lei
L
Cardiac Centre, Beijing Children's Hospital affiliated to Capital Medical University, Beijing 100045, China.
Li
Xiao-Feng
XF
Shen
A-Dong
AD
Wang
Qiang
Q
Liu
Cai-Xia
CX
Guo
Ya-Jie
YJ
Song
Zhen-Jiang
ZJ
Li
Zhong-Zhi
ZZ
D044466:Asian People / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D051792:Basic Helix-Loop-Helix Proteins; C498765:HAND2 protein, human