Homo sapiens Exome

In 2009, we identified a four-generation family with a multigenerational monogenic diabetes from a mountain village in Central China. We performed whole-exome sequencing on four affected individuals (II-1, III-3, III-9 and III-14), who were diagnosed with diabetes at 30, 23, 30 and 35 years of age respectively. About 63,000 variants were identified originally for each case. After filtering against dbSNP v.135 and the 1000 Genomes databases, only 9 protein-altering variants were common to all four cases, of which, only 2 were located conserved elements in genes that probably affected the protein function. Of these 2 variants, only the heterozygous missense mutation in the KCNH6 gene (RefSeq number NM_030779.2: c.704T>C [p.P235L]) on chr17 co-separated with the phenotype when further validated in other family members. We sequenced the KCNH6 gene in a panel of 99 patients with early-onset multigenerational diabetes. We identified two families with heterozygous missense mutation (p.R385G, p.R715W) that were not reported in the public database dbSNP v.135.