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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2019

Open Access 01-12-2019 | Obesity | Research article

Screening of 31 genes involved in monogenic forms of obesity in 23 Pakistani probands with early-onset childhood obesity: a case report

Authors: Robina Khan Niazi, Anette Prior Gjesing, Mette Hollensted, Christian Theil Have, Dmitrii Borisevich, Niels Grarup, Oluf Pedersen, Asmat Ullah, Gulbin Shahid, Ifrah Shafqat, Asma Gul, Torben Hansen

Published in: BMC Medical Genetics | Issue 1/2019

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Abstract

Background

Consanguine families display a high degree of homozygosity which increases the risk of family members suffering from autosomal recessive disorders. Thus, homozygous mutations in monogenic obesity genes may be a more frequent cause of childhood obesity in a consanguineous population.

Methods

We identified 23 probands from 23 Pakistani families displaying autosomal recessive obesity. We have previously excluded mutations in MC4R, LEP and LEPR in all probands. Using a chip-based, target-region capture array, 31 genes involved in monogenic forms of obesity, were screened in all probands.

Results

We identified 31 rare non-synonymous possibly pathogenic variants (28 missense and three nonsense) within the 31 selected genes. All variants were heterozygous, thus no homozygous pathogenic variants were found. Two of the rare heterozygous nonsense variants identified (p.R75X and p.R481X) were found in BBS9 within one proband, suggesting that obesity is caused by compound heterozygosity. Sequencing of the parents supported the compound heterozygous nature of obesity as each parent was carrying one of the variants. Subsequent clinical investigation strongly indicated that the proband had Bardet-Biedl syndrome.

Conclusions

Mutation screening in 31 genes among probands with severe early-onset obesity from Pakistani families did not reveal the presence of homozygous obesity causing variants. However, a compound heterozygote carrier of BBS9 mutations was identified, indicating that compound heterozygosity must not be overlooked when investigating the genetic etiology of severe childhood obesity in populations with a high degree of consanguinity.
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Metadata
Title
Screening of 31 genes involved in monogenic forms of obesity in 23 Pakistani probands with early-onset childhood obesity: a case report
Authors
Robina Khan Niazi
Anette Prior Gjesing
Mette Hollensted
Christian Theil Have
Dmitrii Borisevich
Niels Grarup
Oluf Pedersen
Asmat Ullah
Gulbin Shahid
Ifrah Shafqat
Asma Gul
Torben Hansen
Publication date
01-12-2019
Publisher
BioMed Central
Keywords
Obesity
Obesity
Published in
BMC Medical Genetics / Issue 1/2019
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-019-0886-8

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