The Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in Qatar, a Population-Based Study

<p dir="ltr">Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes mellitus. In this study, we estimated the prevalence and genetic spectrum of MODY in the Middle Eastern population of Qatar using whole-genome sequencing (WGS) of 14,364 subjects from the po...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Asma A. Elashi (17821415) (author)
مؤلفون آخرون: Salman M. Toor (8854751) (author), Ilhame Diboun (3522413) (author), Yasser Al-Sarraj (11721425) (author), Shahrad Taheri (57360) (author), Karsten Suhre (67967) (author), Abdul Badi Abou-Samra (9417977) (author), Omar M. E. Albagha (11704871) (author)
منشور في: 2022
الموضوعات:
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_version_ 1864513512422768640
author Asma A. Elashi (17821415)
author2 Salman M. Toor (8854751)
Ilhame Diboun (3522413)
Yasser Al-Sarraj (11721425)
Shahrad Taheri (57360)
Karsten Suhre (67967)
Abdul Badi Abou-Samra (9417977)
Omar M. E. Albagha (11704871)
author2_role author
author
author
author
author
author
author
author_facet Asma A. Elashi (17821415)
Salman M. Toor (8854751)
Ilhame Diboun (3522413)
Yasser Al-Sarraj (11721425)
Shahrad Taheri (57360)
Karsten Suhre (67967)
Abdul Badi Abou-Samra (9417977)
Omar M. E. Albagha (11704871)
author_role author
dc.creator.none.fl_str_mv Asma A. Elashi (17821415)
Salman M. Toor (8854751)
Ilhame Diboun (3522413)
Yasser Al-Sarraj (11721425)
Shahrad Taheri (57360)
Karsten Suhre (67967)
Abdul Badi Abou-Samra (9417977)
Omar M. E. Albagha (11704871)
dc.date.none.fl_str_mv 2022-12-21T03:00:00Z
dc.identifier.none.fl_str_mv 10.3390/ijms24010130
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/The_Genetic_Spectrum_of_Maturity-Onset_Diabetes_of_the_Young_MODY_in_Qatar_a_Population-Based_Study/26021410
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Genetics
Biomedical and clinical sciences
Clinical sciences
maturity-onset diabetes of the young
MODY
diabetes
HNF1A
HNF4A
GCK
dc.title.none.fl_str_mv The Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in Qatar, a Population-Based Study
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <p dir="ltr">Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes mellitus. In this study, we estimated the prevalence and genetic spectrum of MODY in the Middle Eastern population of Qatar using whole-genome sequencing (WGS) of 14,364 subjects from the population-based Qatar biobank (QBB) cohort. We focused our investigations on 14 previously identified genes ascribed to the cause of MODY and two potentially novel MODY-causing genes, RFX6 and NKX6-1. Genetic variations within the 16 MODY-related genes were assessed for their pathogenicity to identify disease-causing mutations. Analysis of QBB phenotype data revealed 72 subjects (0.5%) with type 1 diabetes, 2915 subjects (20.3%) with type 2 diabetes and 11,377 (79.2%) without diabetes. We identified 22 mutations in 67 subjects that were previously reported in the Human Genetic Mutation Database (HGMD) as disease-causing (DM) or likely disease causing (DM?) for MODY. We also identified 28 potentially novel MODY-causing mutations, predicted to be among the top 1% most deleterious mutations in the human genome, which showed complete (100%) disease penetrance in 34 subjects. Overall, we estimated that MODY accounts for around 2.2–3.4% of diabetes patients in Qatar. This is the first population-based study to determine the genetic spectrum and estimate the prevalence of MODY in the Middle East. Further research to characterize the newly identified mutations is warranted.</p><h2>Other Information</h2><p dir="ltr">Published in: International Journal of Molecular Sciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms24010130" target="_blank">https://dx.doi.org/10.3390/ijms24010130</a></p>
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identifier_str_mv 10.3390/ijms24010130
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/26021410
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spelling The Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in Qatar, a Population-Based StudyAsma A. Elashi (17821415)Salman M. Toor (8854751)Ilhame Diboun (3522413)Yasser Al-Sarraj (11721425)Shahrad Taheri (57360)Karsten Suhre (67967)Abdul Badi Abou-Samra (9417977)Omar M. E. Albagha (11704871)Biological sciencesGeneticsBiomedical and clinical sciencesClinical sciencesmaturity-onset diabetes of the youngMODYdiabetesHNF1AHNF4AGCK<p dir="ltr">Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes mellitus. In this study, we estimated the prevalence and genetic spectrum of MODY in the Middle Eastern population of Qatar using whole-genome sequencing (WGS) of 14,364 subjects from the population-based Qatar biobank (QBB) cohort. We focused our investigations on 14 previously identified genes ascribed to the cause of MODY and two potentially novel MODY-causing genes, RFX6 and NKX6-1. Genetic variations within the 16 MODY-related genes were assessed for their pathogenicity to identify disease-causing mutations. Analysis of QBB phenotype data revealed 72 subjects (0.5%) with type 1 diabetes, 2915 subjects (20.3%) with type 2 diabetes and 11,377 (79.2%) without diabetes. We identified 22 mutations in 67 subjects that were previously reported in the Human Genetic Mutation Database (HGMD) as disease-causing (DM) or likely disease causing (DM?) for MODY. We also identified 28 potentially novel MODY-causing mutations, predicted to be among the top 1% most deleterious mutations in the human genome, which showed complete (100%) disease penetrance in 34 subjects. Overall, we estimated that MODY accounts for around 2.2–3.4% of diabetes patients in Qatar. This is the first population-based study to determine the genetic spectrum and estimate the prevalence of MODY in the Middle East. Further research to characterize the newly identified mutations is warranted.</p><h2>Other Information</h2><p dir="ltr">Published in: International Journal of Molecular Sciences<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/ijms24010130" target="_blank">https://dx.doi.org/10.3390/ijms24010130</a></p>2022-12-21T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/ijms24010130https://figshare.com/articles/journal_contribution/The_Genetic_Spectrum_of_Maturity-Onset_Diabetes_of_the_Young_MODY_in_Qatar_a_Population-Based_Study/26021410CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/260214102022-12-21T03:00:00Z
spellingShingle The Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in Qatar, a Population-Based Study
Asma A. Elashi (17821415)
Biological sciences
Genetics
Biomedical and clinical sciences
Clinical sciences
maturity-onset diabetes of the young
MODY
diabetes
HNF1A
HNF4A
GCK
status_str publishedVersion
title The Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in Qatar, a Population-Based Study
title_full The Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in Qatar, a Population-Based Study
title_fullStr The Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in Qatar, a Population-Based Study
title_full_unstemmed The Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in Qatar, a Population-Based Study
title_short The Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in Qatar, a Population-Based Study
title_sort The Genetic Spectrum of Maturity-Onset Diabetes of the Young (MODY) in Qatar, a Population-Based Study
topic Biological sciences
Genetics
Biomedical and clinical sciences
Clinical sciences
maturity-onset diabetes of the young
MODY
diabetes
HNF1A
HNF4A
GCK