Mutation of RET proto-oncogene in Hirschsprung's disease and intestinal neuronal dysplasia.
OBJECTIVE
To investigate the genetic relationship between Hirschsprung's disease (HD) and intestinal neuronal dysplasia (IND) in Chinese population.


METHODS
Peripheral blood samples were obtained from 30 HD patients, 20 IND patients, 18 HD/IND combined patients and 20 normal individuals as control. Genomic DNA was extracted according to standard procedure. Exons 11,13,15,17 of RET proto-oncogene were amplified by polymerase chain reaction (PCR). The mutations of RET proto-oncogene were analyzed by single strand conformational polymorphism (SSCP) and sequencing of the positive amplified products was performed.


RESULTS
Eight germline sequence variants were detected. In HD patients, 2 missense mutations in exon 11 at nucleotide 15165 G-->A (G667S), 2 frameshift mutations in exon 13 at nucleotide 18974 (18974insG), 1 missense mutation in exon 13 at nucleotide 18919 A-->G (K756E) and 1 silent mutation in exon 15 at nucleotide 20692 G-->A(Q916Q) were detected. In HD/IND combined patients, 1 missense mutation in exon 11 at nucleotide 15165 G-->A and 1 silent mutation in exon 13 at nucleotide 18888 T-->G (L745L) were detected. No mutation was found in IND patients and controls.


CONCLUSIONS
Mutation of RET proto-oncogene is involved in the etiopathogenesis of HD. The frequency of RET proto-oncogene mutation is quite different between IND and HD in Chinese population. IND is a distinct clinical entity genetically different from HD.
Tou
Jin-Fa
JF
Department of Pediatric Surgery, Children's Hospital, Medical College of Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
Li
Min-Ju
MJ
Guan
Tao
T
Li
Ji-Cheng
JC
Zhu
Xiong-Kai
XK
Feng
Zhi-Gang
ZG
D044466:Asian People / Q000235:genetics; D002681:China; D004247:DNA / Q000235:genetics; D017615:Enteric Nervous System / Q000002:abnormalities*; D005091:Exons; D018095:Germ-Line Mutation; D006627:Hirschsprung Disease / Q000209:etiology / Q000235:genetics*; D006801:Humans; D007410:Intestinal Diseases / Q000209:etiology / Q000235:genetics*; D007422:Intestines / Q000294:innervation; D020125:Mutation, Missense; D009474:Neurons / Q000473:pathology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics* / Q000502:physiology
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D004247:DNA; D051096:Proto-Oncogene Proteins c-ret