Mutation of RET gene in Chinese patients with Hirschsprung's disease

AIM:To investigate the pathogenic mechanism ofHirschsprung’s disease(HD)at the molecular level and toelucidate the relationship between RET oncogene andChinese patients with HD.METHODS:Exon 13 of RET oncogene from 20 unrelatedHD patients was analyzed with polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP),Thepositive amplifying products were then sequenced.Accordingto the results of SSCP and DNA sequence,SSCP was doneas well for the samples from the family other members ofsome cases with mutated RET gene.RESULTS:SSCP analysis indicated that mobility abnormalityexisted in 4 unrelated HD patients.Direct DNA sequenceanalysis identified a missense mutation,T to G at thenucleotide 18 888 and a frameshift mutation at the nucleotide18 926 insG.In a HD family,the sicked child and his fatherwere the same heterozygous missense mutation(T to G atnucleotide 18 888).CONCLUSION:Among Chinese HD patients,RET genemutations may exist in considerable proportion withdifferent patterns.These new discoveries indicate that RETmutations may play an important role in the pathogenesisof unrelated HD in the Chinese population.PCR-SSCPcombined with DNA sequence can be used as a tool in thegenetic diagnosis of HD.