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

BMC Medical Genetics

Gulbin Shahid¹  Asmat Ullah²  Ifrah Shafqat³  Asma Gul³  Robina Khan Niazi³  Dmitrii Borisevich⁴  Niels Grarup⁴  Oluf Pedersen⁴  Christian Theil Have⁴  Torben Hansen⁴  Anette Prior Gjesing⁴  Mette Hollensted⁴ 

[1] Children Hospital, Pakistan Institute of Medical Sciences (PIMS);Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University;Department of Biological Sciences, International Islamic University;Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen;

关键词: Autosomal recessive;    Bardet-Biedl syndrome 9;    Compound heterozygous;    Early-onset obesity;    Monogenic obesity;    Pakistani families;   

DOI  :  10.1186/s12881-019-0886-8

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown