Maturity‐onset diabetes of the young as a model for elucidating the multifactorial origin of type 2 diabetes mellitus

• Published in: Journal of diabetes investigation Vol. 9; no. 4; pp. 704 - 712
• Main Author: Horikawa, Yukio
• Format: Journal Article
• Language: English
• Published: Japan John Wiley & Sons, Inc 01.07.2018; John Wiley and Sons Inc
• Subjects: Autosomal dominant inheritance; Basic Helix-Loop-Helix Transcription Factors - genetics; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - etiology; Diabetes Mellitus, Type 2 - genetics; Environmental factors; Hepatocyte Nuclear Factor 1-alpha - genetics; Hepatocyte Nuclear Factor 1-beta - genetics; Hepatocyte Nuclear Factor 4 - genetics; Humans; Maturity‐onset diabetes of the young; Mutation; Pancreas; Penetrance; Phenotype; Phenotypes; Review; Type 2 diabetes mellitus; Penetrance; Maturity-onset diabetes of the young; Type 2 diabetes mellitus
• ISSN: 2040-1116; 2040-1124; 2040-1124
• DOI: 10.1111/jdi.12812

Maturity‐onset diabetes of the young (MODY) is a form of diabetes classically characterized as having autosomal dominant inheritance, onset before the age of 25 years in at least one family member and partly preserved pancreatic β‐cell function. The 14 responsible genes are reported to be MODY type 1~14, of which MODY 2 and 3 might be the most common forms. Although MODY is currently classified as diabetes of a single gene defect, it has become clear that mutations in rare MODYs, such as MODY 5 and MODY 6, have small mutagenic effects and low penetrance. In addition, as there are differences in the clinical phenotypes caused by the same mutation even in the same family, other phenotypic modifying factors are thought to exist; MODY could well have characteristics of type 2 diabetes mellitus, which is of multifactorial origin. Here, we outline the effects of genetic and environmental factors on the known phenotypes of MODY, focusing mainly on the examples of MODY 5 and 6, which have low penetrance, as suggestive models for elucidating the multifactorial origin of type 2 diabetes mellitus.