Molecular Characterization of the Promoter of ATP7B in Wilson Disease / 实用儿科临床杂志

ABSTRACT

Objective To detect molecular characterization of the promoter and 5′UTR region of ATP7B gene in Chinese children with Wilson disease (WD) and explore the distribution of polymorphisms and mutations in different ethnicity.Methods One hundred and ten patients with WD and 90 healthy children were enrolled into the study and analyzed by polymerase chain reaction-single strand configuration polymorphism (PCR-SSCP) and DNA sequence analysis.Results 1.Five polymorphisms were identified as follows, -1294T→G,-105C→G,-116C→T ,-132delGCCGC and -75A→C(transcription start site as +1). The former three ones had never been reported before. The fourth one had not been reported either in China. 2.The polymorphism -132delGCCGC and -75A→C both exhibited with allelic frequency at above 70%, which was much higher than other races. The -132delGCCGC polymorphism shared almost complete linkage disequilibrium with the -75A→C polymorphism (in 98% patients) and their regularity was 96.9%.3. Almost all the polymorphisms distributed in flanking sequence of EXON 1 in Chinese. Race and geological distribution may be dominant factors of the variability of promoter and 5′UTR region of ATP7B gene.Conclusions Three novel polymorphisms and a linkage disequilibrium with the -132delGCCGC and -75A→C were identified in Chinese with WD. It also suggests that the mutation in the promoter of ATP7B is uncommon in Chinese patients.