University of Oulu

Loid P, Pekkinen M, Mustila T, Tossavainen P, Viljakainen H, Lindstrand A and Mäkitie O (2022) Targeted Exome Sequencing of Genes Involved in Rare CNVs in Early-Onset Severe Obesity. Front. Genet. 13:839349. doi: 10.3389/fgene.2022.839349

Targeted exome sequencing of genes involved in rare CNVs in early-onset severe obesity

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Author: Loid, Petra1,2,3; Pekkinen, Minna1,2,3; Mustila, Taina4;
Organizations: 1Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
2Folkhälsan Research Center, Genetics Research Program, Helsinki, Finland
3Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland
4City of Turku Wellfare Services, Diabetes Care, Turku, Finland
5Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, Oulu University Hospital, University of Oulu, Oulu, Finland
6Faculty of Medicine, University of Helsinki, Helsinki, Finland
7Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
8Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: Frontiers Media, 2022
Publish Date: 2022-05-04


Context: Rare copy number variants (CNVs) have been associated with the development of severe obesity. However, the potential disease-causing contribution of individual genes within the region of CNVs is often not known.

Objective: Screening of rare variants in genes involved in CNVs in Finnish patients with severe early-onset obesity to find candidate genes linked to severe obesity.

Methods: Custom-made targeted exome sequencing panel to search for rare (minor allele frequency <0.1%) variants in genes affected by previously identified CNVs in 92 subjects (median age 14 years) with early-onset severe obesity (median body mass index (BMI) Z-score + 4.0).

Results: We identified thirteen rare heterozygous variants of unknown significance in eleven subjects in twelve of the CNV genes. Two rare missense variants (p.Pro405Arg and p.Tyr232Cys) were found in SORCS1, a gene highly expressed in the brain and previously linked to diabetes risk. Four rare variants were in genes in the proximal 16p11.2 region (a frameshift variant in TAOK2 and missense variants in SEZ6L2, ALDOA and KIF22) and three rare missense variants were in genes in the 22q11.21 region (AIFM3, ARVCF and KLHL22).

Conclusion: We report several rare variants in CNV genes in subjects with childhood obesity. However, the role of the individual genes in the previously identified rare CNVs to development of obesity remains uncertain. More studies are needed to understand the potential role of the specific genes within obesity associated CNVs.

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Series: Frontiers in genetics
ISSN: 1664-8021
ISSN-E: 1664-8021
ISSN-L: 1664-8021
Volume: 13
Article number: 839349
DOI: 10.3389/fgene.2022.839349
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3123 Gynaecology and paediatrics
Copyright information: © 2022 Loid, Pekkinen, Mustila, Tossavainen, Viljakainen, Lindstrand and Mäkitie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.