Analysis of Whole Exome Sequencing Results of Type 2 Diabetic Pedigree.
4 affiliations
- 1The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
- 2Kunming Medical University, Kunming, Yunnan, China.
- 3Yunnan University, Kunming, Yunnan, China.
- 4Yunnan Key Laboratory of Laboratory Medicine, Kunming, Yunnan, China.
Abstract
Background
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.Methods
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.Results
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.Conclusion
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.
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BibTeX
@article{chen2026analysis,
title = {{Analysis of Whole Exome Sequencing Results of Type 2 Diabetic Pedigree.}},
author = {Jie Chen and Jia-Li Li and He-Jia Yin and Wei-Chang Guo and Hui-Fang Li},
journal = {Molecular genetics \& genomic medicine},
year = {2026},
month = oct,
doi = {10.1002/mgg3.70296},
url = {https://europepmc.org/article/MED/42904868},
note = {CC BY},
}
RIS
TY - JOUR
TI - Analysis of Whole Exome Sequencing Results of Type 2 Diabetic Pedigree.
AU - Jie Chen
AU - Jia-Li Li
AU - He-Jia Yin
AU - Wei-Chang Guo
AU - Hui-Fang Li
PY - 2026
DA - 2026/10/01
JO - Molecular genetics & genomic medicine
DO - 10.1002/mgg3.70296
UR - https://europepmc.org/article/MED/42904868
AB - Background 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.Methods 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.Results 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.Conclusion 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.
SN - 2324-9269
ER -