Background: Type 2 diabetes mellitus (T2DM) is characterized by β cell decline in the pancreas and insulin resistance. This study aimed to investigate the possible pathogenic gene mutation sites of T2DM patients using whole exome sequencing.
Materials and Methods: We recruited a Chinese family with 3-generation history of diabetes. The whole blood genomic DNA of seven members of the family was extracted and sent for whole exome sequencing. Biological information was analyzed with in silico prediction methods, including significance analysis of single nucleotide polymorphism (SNP)/Indel site, and analysis of specific SNP/Indel proteins and their potential mechanisms.
Results: Six out of seven members of the family were diagnosed with diabetes. All DNA samples (23 kb) met quality requirements of library construction. Clean reads of each sample demonstrated high Q20 and Q30 (> 80%), indicating good sequencing quality of sequencing data. A total of 130,693 SNPs and 15,928 Indels were found in DNA samples. A total of 22 significant SNPs and Indel mutation sites located on 19 genes were obtained, including ZCCHC3, SYN2, RPL14, SRRD, AMD1, CAMKK2, ZNF787, RNF157, NPIPB15, ALG3, KIAA0040, MAST2, ESRRA, C8orf58, PNLIPRP1, DACH1, MACC1, CAPN9  and DMKN . An rs2305205  mutation of PNLIPRP1  gene and an rs778701848  mutation of CAMKK2  gene may be associated with the pathogenesis of T2DM in this family.
Conclusion: Exons of these diabetic patients demonstrated an rs2305205  mutation in PNLIPRP1  gene and an rs778701848  mutation in CAMKK2  gene. These two mutations might promote T2DM occurrence through reducing sensitivity of peripheral tissue to insulin and reducing insulin secretion.
Keywords: type 2 diabetes, gene mutation, whole exome sequencing, PNLIPRP1 , CAMKK2