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. 2023 Mar 7;12(3):413.
doi: 10.3390/biology12030413.

Whole-Exome Sequencing in Family Trios Reveals De Novo Mutations Associated with Type 1 Diabetes Mellitus

Mira Mousa  1 , Sara Albarguthi  1   2 , Mohammed Albreiki  1 , Zenab Farooq  3 , Sameeha Sajid  3 , Sarah El Hajj Chehadeh  1 , Gihan Daw ElBait  1 , Guan Tay  1 , Asma Al Deeb  3   4 , Habiba Alsafar  1   2
Affiliations

Whole-Exome Sequencing in Family Trios Reveals De Novo Mutations Associated with Type 1 Diabetes Mellitus

Mira Mousa et al. Biology (Basel). .

Abstract

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by insulin deficiency and loss of pancreatic islet β-cells. The objective of this study is to identify de novo mutations in 13 trios from singleton families that contribute to the genetic basis of T1DM through the application of whole-exome sequencing (WES). Of the 13 families sampled for this project, 12 had de novo variants, with Family 7 having the highest number (nine) of variants linked to T1DM/autoimmune pathways, whilst Family 4 did not have any variants past the filtering steps. There were 10 variants of 7 genes reportedly associated with T1DM (MST1; TDG; TYRO3; IFIHI; GLIS3; VEGFA; TYK2). There were 20 variants of 13 genes that were linked to endocrine, metabolic, or autoimmune diseases. Our findings demonstrate that trio-based WES is a powerful approach for identifying new candidate genes for the pathogenesis of T1D. Genotyping and functional annotation of the discovered de novo variants in a large cohort is recommended to ascertain their association with disease pathogenesis.

Keywords: T1D; WES; case–parent trios; de novo variants; diabetes; family trios; type 1 diabetes.

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Conflict of interest statement

The authors declare no conflict of interest.

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