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Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence in an Inbred Population of Pakistan.
Saeed, Sadia; Arslan, Muhammad; Manzoor, Jaida; Din, Sadia M; Janjua, Qasim M; Ayesha, Hina; Ain, Qura-Tul; Inam, Laraib; Lobbens, Stephane; Vaillant, Emmanuel; Durand, Emmanuelle; Derhourhi, Mehdi; Amanzougarene, Souhila; Badreddine, Alaa; Berberian, Lionel; Gaget, Stefan; Khan, Waqas I; Butt, Taeed A; Bonnefond, Amélie; Froguel, Philippe.
Afiliación
  • Saeed S; Université de Lille, INSERM UMR1283, CNRS-UMR 8199-European Genomic Institute for Diabetes, and Lille University Hospital, Lille, France.
  • Arslan M; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, U.K.
  • Manzoor J; School of Life Sciences, Forman Christian College (A Chartered University), Lahore, Pakistan.
  • Din SM; Department of Paediatric Endocrinology, Children's Hospital, Lahore, Pakistan.
  • Janjua QM; Institute of Molecular Biology and Biotechnology, University of Lahore, Lahore, Pakistan.
  • Ayesha H; Institute of Molecular Biology and Biotechnology, University of Lahore, Lahore, Pakistan.
  • Ain QT; Department of Physiology, University College of Medicine and Dentistry, University of Lahore, Lahore, Pakistan.
  • Inam L; Department of Paediatrics, Punjab Medical College, Faisalabad, Pakistan.
  • Lobbens S; Institute of Molecular Biology and Biotechnology, University of Lahore, Lahore, Pakistan.
  • Vaillant E; School of Life Sciences, Forman Christian College (A Chartered University), Lahore, Pakistan.
  • Durand E; Université de Lille, INSERM UMR1283, CNRS-UMR 8199-European Genomic Institute for Diabetes, and Lille University Hospital, Lille, France.
  • Derhourhi M; Université de Lille, INSERM UMR1283, CNRS-UMR 8199-European Genomic Institute for Diabetes, and Lille University Hospital, Lille, France.
  • Amanzougarene S; Université de Lille, INSERM UMR1283, CNRS-UMR 8199-European Genomic Institute for Diabetes, and Lille University Hospital, Lille, France.
  • Badreddine A; Université de Lille, INSERM UMR1283, CNRS-UMR 8199-European Genomic Institute for Diabetes, and Lille University Hospital, Lille, France.
  • Berberian L; Université de Lille, INSERM UMR1283, CNRS-UMR 8199-European Genomic Institute for Diabetes, and Lille University Hospital, Lille, France.
  • Gaget S; Université de Lille, INSERM UMR1283, CNRS-UMR 8199-European Genomic Institute for Diabetes, and Lille University Hospital, Lille, France.
  • Khan WI; Université de Lille, INSERM UMR1283, CNRS-UMR 8199-European Genomic Institute for Diabetes, and Lille University Hospital, Lille, France.
  • Butt TA; Université de Lille, INSERM UMR1283, CNRS-UMR 8199-European Genomic Institute for Diabetes, and Lille University Hospital, Lille, France.
  • Bonnefond A; The Children Hospital and the Institute of Child Health, Multan, Pakistan.
  • Froguel P; Department of Pediatrics, Fatima Memorial Hospital, Lahore, Pakistan.
Diabetes ; 69(7): 1424-1438, 2020 07.
Article en En | MEDLINE | ID: mdl-32349990
Monogenic forms of obesity have been identified in ≤10% of severely obese European patients. However, the overall spectrum of deleterious variants (point mutations and structural variants) responsible for childhood severe obesity remains elusive. In this study, we genetically screened 225 severely obese children from consanguineous Pakistani families through a combination of techniques, including an in-house-developed augmented whole-exome sequencing method (CoDE-seq) that enables simultaneous detection of whole-exome copy number variations (CNVs) and point mutations in coding regions. We identified 110 (49%) probands carrying 55 different pathogenic point mutations and CNVs in 13 genes/loci responsible for nonsyndromic and syndromic monofactorial obesity. CoDE-seq also identified 28 rare or novel CNVs associated with intellectual disability in 22 additional obese subjects (10%). Additionally, we highlight variants in candidate genes for obesity warranting further investigation. Altogether, 59% of cases in the studied cohort are likely to have a discrete genetic cause, with 13% of these as a result of CNVs, demonstrating a remarkably higher prevalence of monofactorial obesity than hitherto reported and a plausible overlapping of obesity and intellectual disabilities in several cases. Finally, inbred populations with a high prevalence of obesity provide unique, genetically enriched material in the quest of new genes/variants influencing energy balance.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Obesidad Mórbida / Obesidad Infantil Tipo de estudio: Etiology_studies / Prevalence_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Diabetes Año: 2020 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Obesidad Mórbida / Obesidad Infantil Tipo de estudio: Etiology_studies / Prevalence_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Diabetes Año: 2020 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos