Mutation screening of epithelial sodium channel gene in a Liddle's syndrome family / 中华肾脏病杂志

ABSTRACT

Objective To screen the mutation in P and 7 subunit of epithelial sodium channel (ENaC) gene in the relatives of a patient diagnosed as Liddle's syndrome. Methods In a family of three generations, seven family members were affected with hypertension, among them a girl aged 14 years was diagnosed as Laddie's syndrome and her mother and maternal grandsire died of stroke at thirty-eight years. Peripheral blood samples were collected from all living members of the family and total genomic DNA was prepared for genetic analysis. Polymerase chain reaction (PCR) was used for amplifying the final exon of the ? ENaC (codon 513-638) and ? ENaC (codon 524-631 )gene. PCR products were purified and subjected to direct DNA sequencing. Results Genetic analysis of the ? ENaC gene revealed a missense mutation of CCC (Pro) to TCC (Ser)at codon 616 in the index case and two other family members. In these three family members, a new variant of GAC (Asp) to CAC(His) at codon 632 was found, which was linked with 616 (Ser) . This variant was not detected by direct sequencing the final exon of ? ENaC gene in 150 unrelated subjects. Through clinical examinations and biochemical measurement, thSese two mutation carriers' biochemical characteristics were all concordant with Liddle's syndrome. Neither mutation could be detected in other members of this family. The mutation TGG(Trp)573TAG(Term) of ? ENaC gene could not be found in this family either. Conclusions (1) Screening for specific mutations of ENaC in relatives of patients affected with Liddle's syndrome can be used to identify previously unrecognized cases within families. (2) A new missense mutation in the ? ENaC gene is found in this family.