[Mutation and expression of WNT8b gene and SHH gene in Hirschsprung disease].
OBJECTIVE
To investigate the relationship of WNT8b and SHH genes mutation and Hirschsprung disease(HSCR) in Chinese children.


METHODS
Preoperative whole blood preparations in 72 children with sporadic HSCR from northeast China were collected(study group). Seventy-two healthy children were used as controls(matched for sex and age). Genomic DNA was obtained from peripheral blood. Exon 1 of WNT8b gene and the exon 1 of SHH gene were analyzed for gene mutation. The mutation products were automatically sequenced. The levels of WNT8b and SHH mRNA were detected by quantitative real-time PCR(qRT-PCR) in blood samples.


RESULTS
On sequencing, 13 out of 72 children with HSCR had WNT8b gene mutation in the coding area, including heterozygosity deletion in 8 cases (11.1%) and base replacement in 5(6.9%). Eleven children with HSCR had SHH gene mutation in the coding area including heterozygosity deletion in 7 cases(9.7%) and base replacement in 4(5.6%). No mutations in WNT8b and SHH genes were found in the control group. The WNT8b and SHH mRNA levels were different between the study group and the control group(30.01±1.13 vs. 17.33±0.62, and 28.25±1.27 vs. 18.94±0.31, P<0.05).


CONCLUSIONS
WNT8b and SHH mutations and abnormal expressions are present in the peripheral blood of children with sporadic HSCR. These two genes may be related to the development of sporadic HSCR in children in the northeastern China.
Key Laboratory of Congenital Malformation Reseach, The Ministry of Health, Shengjing Affiliated Hospital, China Medical University, Shenyang 110004, China. gaohong515@sina.com
Hong
H
Gao
Zhi-bo
ZB
Zhang
Zhong-jia
ZJ
Jiang
Da-jia
DJ
Wang
Ying
Y
Huang
Wei-lin
WL
Wang
D000293:Adolescent; D001483:Base Sequence; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005091:Exons; D005260:Female; D053823:Hedgehog Proteins / Q000235:genetics*; D006579:Heterozygote; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D051153:Wnt Proteins / Q000235:genetics*
D053823:Hedgehog Proteins; C509239:SHH protein, human; C490604:WNT8B protein, human; D051153:Wnt Proteins