Mutation of RET gene in Chinese patients with Hirschsprung's disease.
OBJECTIVE
To investigate the pathogenic mechanism of Hirschsprung's disease (HD) at the molecular level and to elucidate the relationship between RET oncogene and Chinese patients with HD.


METHODS
Exon 13 of RET oncogene from 20 unrelated HD patients was analyzed with polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). The positive amplifying products were then sequenced. According to the results of SSCP and DNA sequence, SSCP was done as well for the samples from the family other members of some cases with mutated RET gene.


RESULTS
SSCP analysis indicated that mobility abnormality existed in 4 unrelated HD patients. Direct DNA sequence analysis identified a missense mutation, T to G at the nucleotide 18 888 and a frameshift mutation at the nucleotide 18 926 insG. In a HD family, the sicked child and his father were the same heterozygous missense mutation (T to G at nucleotide 18 888).


CONCLUSIONS
Among Chinese HD patients, RET gene mutations may exist in considerable proportion with different patterns. These new discoveries indicate that RET mutations may play an important role in the pathogenesis of unrelated HD in the Chinese population. PCR-SSCP combined with DNA sequence can be used as a tool in the genetic diagnosis of HD.
Li
Ji-Cheng
JC
Department of Lymphology, Department of Histology and Embryology, Zhejiang University Medical College, Hangzhou 310031, Zhejiang Province, China. lijc@mail.hz.zj.cn
Ding
Shi-Ping
SP
Song
Ying
Y
Li
Min-Ju
MJ
D001483:Base Sequence; D002681:China; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D006627:Hirschsprung Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
D015513:Oncogene Proteins; D004247:DNA; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases