Comprehensive genetic screening: The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort

Stephanie R. Johnson, Jonathan J. Ellis, Paul J. Leo, Lisa K. Anderson, Uma Ganti, Jessica E. Harris, Jacqueline A. Curran, Aideen M. McInerney-Leo, Nirubasini Paramalingam, Xiaoxia Song, Louise S. Conwell, Mark Harris, Timothy W. Jones, Matthew A. Brown, Elizabeth A. Davis, Emma L. Duncan

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2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalPediatric Diabetes
Volume20
Issue number1
DOIs
Publication statusPublished - 1 Feb 2019

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Genetic Testing
Population
Genes
Pediatrics
Mason-Type Diabetes
High-Throughput Nucleotide Sequencing
Western Australia
Antibodies
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Mutation
DNA

Cite this

Johnson, Stephanie R. ; Ellis, Jonathan J. ; Leo, Paul J. ; Anderson, Lisa K. ; Ganti, Uma ; Harris, Jessica E. ; Curran, Jacqueline A. ; McInerney-Leo, Aideen M. ; Paramalingam, Nirubasini ; Song, Xiaoxia ; Conwell, Louise S. ; Harris, Mark ; Jones, Timothy W. ; Brown, Matthew A. ; Davis, Elizabeth A. ; Duncan, Emma L. / Comprehensive genetic screening : The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort. In: Pediatric Diabetes. 2019 ; Vol. 20, No. 1. pp. 57-64.
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title = "Comprehensive genetic screening: The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort",
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.",
keywords = "childhood diabetes, genetic testing, massively parallel sequencing, maturity-onset diabetes of the young, prevalence",
author = "Johnson, {Stephanie R.} and Ellis, {Jonathan J.} and Leo, {Paul J.} and Anderson, {Lisa K.} and Uma Ganti and Harris, {Jessica E.} and Curran, {Jacqueline A.} and McInerney-Leo, {Aideen M.} and Nirubasini Paramalingam and Xiaoxia Song and Conwell, {Louise S.} and Mark Harris and Jones, {Timothy W.} and Brown, {Matthew A.} and Davis, {Elizabeth A.} and Duncan, {Emma L.}",
year = "2019",
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Johnson, SR, Ellis, JJ, Leo, PJ, Anderson, LK, Ganti, U, Harris, JE, Curran, JA, McInerney-Leo, AM, Paramalingam, N, Song, X, Conwell, LS, Harris, M, Jones, TW, Brown, MA, Davis, EA & Duncan, EL 2019, 'Comprehensive genetic screening: The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort' Pediatric Diabetes, vol. 20, no. 1, pp. 57-64. https://doi.org/10.1111/pedi.12766

Comprehensive genetic screening : The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort. / Johnson, Stephanie R.; Ellis, Jonathan J.; Leo, Paul J.; Anderson, Lisa K.; Ganti, Uma; Harris, Jessica E.; Curran, Jacqueline A.; McInerney-Leo, Aideen M.; Paramalingam, Nirubasini; Song, Xiaoxia; Conwell, Louise S.; Harris, Mark; Jones, Timothy W.; Brown, Matthew A.; Davis, Elizabeth A.; Duncan, Emma L.

In: Pediatric Diabetes, Vol. 20, No. 1, 01.02.2019, p. 57-64.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comprehensive genetic screening

T2 - The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort

AU - Johnson, Stephanie R.

AU - Ellis, Jonathan J.

AU - Leo, Paul J.

AU - Anderson, Lisa K.

AU - Ganti, Uma

AU - Harris, Jessica E.

AU - Curran, Jacqueline A.

AU - McInerney-Leo, Aideen M.

AU - Paramalingam, Nirubasini

AU - Song, Xiaoxia

AU - Conwell, Louise S.

AU - Harris, Mark

AU - Jones, Timothy W.

AU - Brown, Matthew A.

AU - Davis, Elizabeth A.

AU - Duncan, Emma L.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - 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.

AB - 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.

KW - childhood diabetes

KW - genetic testing

KW - massively parallel sequencing

KW - maturity-onset diabetes of the young

KW - prevalence

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