Molecular genetic etiology by whole exome sequence analysis in cases with familial type 1 diabetes mellitus without HLA haplotype predisposition or incomplete predisposition

• DOI: 10.1515/jpem-2022-0295
• Publication Date: 2022-11-07T20:59:28Z
• Authors: Uğur Cem Yilmaz; Ferda Evin; Huseyin Onay; Samim Ozen; Sukran Darcan; Damla Goksen Simsek
• Keywords: Genetic predisposition; Etiology; Exome; Sequence (biology)

Abstract Objectives Familial transmission is observed in approximately 10% of cases with type 1 diabetes mellitus (T1DM). The most important gene determining susceptibility the human leukocyte antigen complex (HLA) located on chromosome 6. More than 50 susceptible loci are associated T1DM have been identified genes other HLA. In this study, it was aimed to investigate molecular genetic etiology by whole-exome sequence (WES) analysis familial no or weakly detected HLA tissue susceptibility. We identify new responsible for development and reveal that not shown literature before. Methods Cases at least one diagnosis first-degree relatives were included study. first step, DQ2 DQ8 loci, which known be susceptibility, investigated by. second presence variants could explain situation WES patients who negative both haplotypes, negative, positive, positive patients. Results mean age duration 30 (Girl/Male: 17/13) 14.9 ± 6 7.56 3.84 years, respectively. There consanguineous marriage 5 (16%) families. As a result filtering all exome data two (DQB1*02) (−) (DQB1*03:02) (−), seven (+) case (+), different five cases. pathogenicity determined according “American College Medical Genetics Genomics (ACMG)” criteria. These evaluated as high-score VUS (Variants unknown/uncertain significance). segregation study conducted mutation POLG 5, variant mother his brother T1DM. Segregation studies ongoing affected individuals family. Conclusions conclusion, weak VUS. might novel candidate Non-HLA directly any