Copy Number Variants Are Enriched in Individuals With Early-Onset Obesity and Highlight Novel Pathogenic Pathways

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http://hdl.handle.net/10138/297909

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Pettersson , M , Viljakainen , H , Loid , P , Mustila , T , Pekkinen , M , Armenio , M , Andersson-Assarsson , J C , Makitie , O & Lindstrand , A 2017 , ' Copy Number Variants Are Enriched in Individuals With Early-Onset Obesity and Highlight Novel Pathogenic Pathways ' , Journal of Clinical Endocrinology and Metabolism , vol. 102 , no. 8 , pp. 3029-3039 . https://doi.org/10.1210/jc.2017-00565

Title: Copy Number Variants Are Enriched in Individuals With Early-Onset Obesity and Highlight Novel Pathogenic Pathways
Author: Pettersson, Maria; Viljakainen, Heli; Loid, Petra; Mustila, Taina; Pekkinen, Minna; Armenio, Miriam; Andersson-Assarsson, Johanna C.; Makitie, Outi; Lindstrand, Anna
Contributor: University of Helsinki, Clinicum
University of Helsinki, Clinicum
University of Helsinki, Clinicum
Date: 2017-08
Language: eng
Number of pages: 11
Belongs to series: Journal of Clinical Endocrinology and Metabolism
ISSN: 0021-972X
URI: http://hdl.handle.net/10138/297909
Abstract: Context: Only a few genetic causes for childhood obesity have been identified to date. Copy number variants (CNVs) are known to contribute to obesity, both syndromic (15q11.2 deletions, Prader-Willi syndrome) and nonsyndromic (16p11.2 deletions) obesity. Objective: To study the contribution of CNVs to early-onset obesity and evaluate the expression of candidate genes in subcutaneous adipose tissue. Design and Setting: A case-control study in a tertiary academic center. Participants: CNV analysis was performed on 90 subjects with early-onset obesity and 67 normalweight controls. Subcutaneous adipose tissue from body mass index-discordant siblings was used for the gene expression analyses. Main Outcome Measures: We used custom high-density array comparative genomic hybridization with exon resolution in 1989 genes, including all known obesity loci. The expression of candidate genes was assessed using microarray analysis of messenger RNA from subcutaneous adipose tissue. Results: We identified rare CNVs in 17 subjects (19%) with obesity and 2 controls (3%). In three cases (3%), the identified variant involved a known syndromic lesion (22q11.21 duplication, 1q21.1 deletion, and 16p11.2 deletion, respectively), although the others were not known. Seven CNVs in 10 families were inherited and segregated with obesity. Expression analysis of 37 candidate genes showed discordant expression for 10 genes (PCM1, EFEMP1, MAMLD1, ACP6, BAZ2B, SORBS1, KLF15, MACROD2, ATR, and MBD5). Conclusions: Rare CNVs contribute possibly pathogenic alleles to a substantial fraction of children with early-onset obesity. The involved genes might provide insights into pathogenic mechanisms and involved cellular pathways. These findings highlight the importance of CNV screening in children with early-onset obesity.
Subject: BARDET-BIEDL-SYNDROME
ASSOCIATION
DELETIONS
TYPE-2
LOCI
REARRANGEMENTS
CONTRIBUTES
POPULATION
MUTATIONS
INSIGHTS
3121 General medicine, internal medicine and other clinical medicine
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