Stephanie R Johnson1,2,3,4, Jonathan J Ellis2, Paul J Leo2, Lisa K Anderson2, Uma Ganti5,6, Jessica E Harris2, Jacqueline A Curran5,6, Aideen M McInerney-Leo2,4, Nirubasini Paramalingam5,6, Xiaoxia Song2, Louise S Conwell1,3, Mark Harris1,3,4, Timothy W Jones5,6,7, Matthew A Brown2, Elizabeth A Davis5,6,7, Emma L Duncan2,3,8. 1. Department of Endocrinology and Diabetes, Lady Cilento Children's Hospital, South Brisbane, Queensland, Australia. 2. Institute of Health and Biomedical Innovation, Faculty of Health, Queensland University of Technology (QUT), Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia. 3. Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia. 4. University of Queensland Diamantina Institute, Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia. 5. Department of Endocrinology and Diabetes, Perth Children's Hospital, Perth, Western Australia, Australia. 6. Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia. 7. School of Medicine, University of Western Australia, Perth, Western Australia, Australia. 8. Department of Endocrinology and Diabetes, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
Abstract
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.
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.
Authors: Lewis Pang; Kevin C Colclough; Maggie H Shepherd; Joanne McLean; Ewan R Pearson; Sian Ellard; Andrew T Hattersley; Beverley M Shields Journal: Diabetes Care Date: 2022-03-01 Impact factor: 19.112
Authors: Annelie Carlsson; Maggie Shepherd; Sian Ellard; Michael Weedon; Åke Lernmark; Gun Forsander; Kevin Colclough; Qefsere Brahimi; Camilla Valtonen-Andre; Sten A Ivarsson; Helena Elding Larsson; Ulf Samuelsson; Eva Örtqvist; Leif Groop; Johnny Ludvigsson; Claude Marcus; Andrew T Hattersley Journal: Diabetes Care Date: 2019-11-08 Impact factor: 19.112
Authors: Sarah M Graff; Stephanie R Johnson; Paul J Leo; Prasanna K Dadi; Matthew T Dickerson; Arya Y Nakhe; Aideen M McInerney-Leo; Mhairi Marshall; Karolina E Zaborska; Charles M Schaub; Matthew A Brown; David A Jacobson; Emma L Duncan Journal: JCI Insight Date: 2021-07-08