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Comprehensive genetic screening: The prevalence of maturity‐onset diabetes of the young gene variants in a population‐based childhood diabetes cohort
Author(s) -
Johnson Stephanie R.,
Ellis Jonathan J.,
Leo Paul J.,
Anderson Lisa K.,
Ganti Uma,
Harris Jessica E.,
Curran Jacqueline A.,
McInerneyLeo Aideen M.,
Paramalingam Nirubasini,
Song Xiaoxia,
Conwell Louise S.,
Harris Mark,
Jones Timothy W.,
Brown Matthew A.,
Davis Elizabeth A.,
Duncan Emma L.
Publication year - 2019
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1111/pedi.12766
Subject(s) - medicine , cohort , population , diabetes mellitus , cohort study , maturity onset diabetes of the young , pediatrics , genetic testing , type 2 diabetes , type 1 diabetes , endocrinology , environmental health
Background Maturity‐onset diabetes of the young (MODY) is caused by autosomal dominant mutations in one of 13 confirmed genes. Estimates of MODY prevalence vary widely, as genetic screening is usually restricted based on clinical features, even in population studies. We aimed to determine prevalence of MODY variants in a large and unselected pediatric diabetes cohort. Methods MODY variants were assessed using massively parallel sequencing in the population‐based diabetes cohort (n = 1363) of the sole tertiary pediatric diabetes service for Western Australia (population 2.6 million). All individuals were screened, irrespective of clinical features. MODY variants were also assessed in a control cohort (n = 993). Results DNA and signed consent were available for 821 children. Seventeen children had pathogenic/likely pathogenic variants in MODY genes, two diagnosed with type 2 diabetes, four diagnosed with antibody‐negative type 1 diabetes (T1DM), three diagnosed with antibody‐positive T1DM, and eight previously diagnosed with MODY. Prevalence of MODY variants in the sequenced cohort was 2.1%, compared to 0.3% of controls. Conclusions This is the first comprehensive study of MODY variants in an unselected population‐based pediatric diabetes cohort. The observed prevalence, increasing access to rapid and affordable genetic screening, and significant clinical implications suggest that genetic screening for MODY could be considered for all children with diabetes, irrespective of other clinical features.