Analysis of Whole Exome Sequencing Results of Type 2 Diabetic Pedigree

Type 2 diabetes mellitus (T2DM) exhibits strong familial aggregation. This study aimed to identify potential pathogenic genes and mutation sites in a Chinese pedigree with a high prevalence of T2DM.

A multigenerational family with 20 members, including 5 diagnosed with T2DM, was enrolled. The proband was a second-generation female with a 10-year disease history. Peripheral blood was collected, genomic DNA was extracted from blood cells, and whole exome sequencing was performed. Bioinformatic analysis, including KEGG pathway mapping, was used to screen candidate pathogenic variants.

Sequencing revealed 485 DNA variants, which were filtered to 16 high-priority mutations (15 SNPs and 1 Indel). Through literature review and functional pathway analysis, two heterozygous mutations-EPHX3 rs760409070 [c.778G>A, p.Glu260Lys] and FHOD1 rs142023201 [c.1493A>G, p.Asn498Ser]-were identified as candidate pathogenic variants. These two mutations were consistently present in all affected family members.

The EPHX3 rs760409070 and FHOD1 rs142023201 mutations are likely contributing genetic factors to T2DM in this pedigree. Based on bioinformatic analysis, we hypothesize that these mutations may promote diabetes pathogenesis by reducing peripheral insulin sensitivity, impairing glucose uptake, suppressing glycogen synthesis, and enhancing gluconeogenesis.