Monogenic Diabetes

Gene: DYRK1B

I don't know

Have reviewed as Amber based on metabolic syndrome phenotype having a significant polygenic contribution, prevalence of reported variants in healthy population databases and inconclusive functional evidence.

PMID 24827035 Keramati et al 2014 NEJM - first reported a heterozygous DYRK1B founder variant (R102C) in 3 Iranian families with early-onset features of metabolic syndrome (central obesity, coronary artery disease, T2DM, hypertension, hypertriglyceridemia). Variant identified by WES and co-segregated with this phenotype in the family. Variant present in gnomad (v2) - 4 hets (European Non-Finnish), 40-45 yo age group. The authors also screened a cohort of 300 morbidly obese Caucasian individuals for this variant and identified heterozygous H90C variant (same exon) in 5 individuals. These individuals also had features of early-onset metabolic syndrome with variant reported to co-segregate with this phenotype in the family. This variant is absent from gnomAD. Functional studies in this study and PMID 28743892 have been inconclusive in clarifying the gene disease mechanism for this variant.

PMID 34193236 Mendoza-Caamal et al 2021 - report 2 unrelated families with heterozygous variants in this gene co-segregating with early-onset metabolic syndrome phenotype. p.Arg252His variant present in 8 hets in gnomAD and p.Lys68Gln in 5 hets.

PMID 34786696 Orenstein et al 2022 report a family with DYRK1B PTC variant associated with metabolic syndrome and abnormal cognition - unable to access this article.

Created: 4 May 2022, 2:02 a.m. | Last Modified: 4 May 2022, 2:02 a.m.

Panel Version: 0.23

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Abdominal obesity-metabolic syndrome 3 - MIM#615812

Publications

• 34193236
• 34786696
• 24827035
• 28743892