Comprehensive genetic screening : The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Pediatric diabetes - 20(2019), 1 vom: 12. Feb., Seite 57-64 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Johnson, Stephanie R [VerfasserIn] |
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| Links: |
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| Themen: |
Childhood diabetes |
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| Anmerkungen: |
Date Completed 19.08.2019 Date Revised 19.08.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/pedi.12766 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM288290895 |
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| 100 | 1 | |a Johnson, Stephanie R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Comprehensive genetic screening |b The prevalence of maturity-onset diabetes of the young gene variants in a population-based childhood diabetes cohort |
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| 500 | |a Date Revised 19.08.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a childhood diabetes | |
| 650 | 4 | |a genetic testing | |
| 650 | 4 | |a massively parallel sequencing | |
| 650 | 4 | |a maturity-onset diabetes of the young | |
| 650 | 4 | |a prevalence | |
| 700 | 1 | |a Ellis, Jonathan J |e verfasserin |4 aut | |
| 700 | 1 | |a Leo, Paul J |e verfasserin |4 aut | |
| 700 | 1 | |a Anderson, Lisa K |e verfasserin |4 aut | |
| 700 | 1 | |a Ganti, Uma |e verfasserin |4 aut | |
| 700 | 1 | |a Harris, Jessica E |e verfasserin |4 aut | |
| 700 | 1 | |a Curran, Jacqueline A |e verfasserin |4 aut | |
| 700 | 1 | |a McInerney-Leo, Aideen M |e verfasserin |4 aut | |
| 700 | 1 | |a Paramalingam, Nirubasini |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Xiaoxia |e verfasserin |4 aut | |
| 700 | 1 | |a Conwell, Louise S |e verfasserin |4 aut | |
| 700 | 1 | |a Harris, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Jones, Timothy W |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Matthew A |e verfasserin |4 aut | |
| 700 | 1 | |a Davis, Elizabeth A |e verfasserin |4 aut | |
| 700 | 1 | |a Duncan, Emma L |e verfasserin |4 aut | |
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