Genetic analysis and clinical features of familial hypokalemic periodic paralysis

Background To investigate the gene mutation and clinical features of hypokalemic periodic paralysis (HypoPP) in a Han family. Methods Mutation analyses of CACNA1S , SCN4A and KCNE3 gene were screened by DNA direct sequencing in the proband (Ⅲ3). Then, other patients and one asymptomatic relative were tested for the mutation detected in the proband before. Besides, clinical information was collected and analyzed carefully so as to detect whether the mutations were responsible for HypoPP.  Results KCNE3 gene was not detected in the propositus (Ⅲ 3). Mutations of IVS25-194C/T in CACNA1S gene were detected in the propositus (Ⅲ 3) and other patients (Ⅱ 1, Ⅲ 4, Ⅳ 3), while it was not detected in the asymptomatic relative (Ⅲ1). Given that it was an intron mutation, we presumed that it was not responsible for HypoPP in this family. In addition, mutations of IVS18-130G/A in SCN4A gene were detected in all patients (except for Ⅰ1) and asymptomatic relative (Ⅲ 1). Since it was an intron mutation and it was detected in symptomatic or asymptomatic members simultaneously, we also presumed that it was not responsible for HypoPP in this family. Interestingly, a missense mutation (V662I) of c.1984G > A in exon 12 of SCN4A gene was detected in the proband (Ⅲ 3) and asymptomatic relative (Ⅲ 1). However, it was not detected in other symptomatic members ( Ⅱ 1, Ⅲ 4, Ⅳ 3). Based on clinical information and bioinformatics, we presumed that it was not causative mutation for the disease in this pedigree. Conclusions This pedigree research enriched the data of gene mutation and clinical features of HypoPP in China. Besides for gene KCNE3 , CACNA1S and SCN4A , other gene mutations accounted for HypoPP in the Han family should be further studied. doi: 10.3969/j.issn.1672-6731.2014.06.006