The genetic elucidation of monogenic obesity in the Arab world: a systematic review

Abstract

Background Investigation of monogenic obesity (MO), a rare condition caused by a single gene variant(s), especially in consanguineous populations, is a powerful approach for obtaining novel insights into the genetic alterations involved. Here, we present a systematic review of the genetics of MO in the 22 Arab countries and apply protein modeling in silico to the missense variants reported. Methods We searched four literature databases (PubMed, Web of Science, Science Direct and Scopus) from the time of their first creation until December 2020, utilizing broad search terms to capture all genetic studies related to MO in the Arab countries. Only articles published in peer-reviewed journals involving subjects from at least one of the 22 Arab countries and dealing with genetic variants related to MO were included. Protein modelling of the variants identified was performed using PyMOL. Results The 30 cases with severe early-onset obesity identified in 13 studies carried 14 variants in five genes (LEP, LEPR, POMC, MC4R and CPE). All of these variants were pathogenic, homozygous and carried by members of consanguineous families. Conclusion Despite the elevated presence of consanguinity in the Arab countries, the genetic origins of MO remain largely unexplained and require additional studies, both of a genetic and functional character.

Sequencing methods, functional characterization, prevalence, and penetrance of rare coding mutations in panels of monogenic obesity genes from the leptin‐melanocortin pathway: A systematic review

“…The distribution of heterozygous and homozygous mutations identified in obesity case series is consistent with the mode of inheritance for monogenic obesity in these genes: autosomal dominant ( SIM1 , BDNF , NTRK2 ), autosomal recessive ( LEPR , LEP , ADCY3 ), autosomal additive ( POMC , PCSK1 , MC4R , MC3R ) 39 . Unsurprisingly, homozygous carriers of mutations were more frequent in endogamic populations, such as Pakistan, Turkey, and Qatar 63,64 . Homozygous carriers of mutations in the SIM1 , BDNF , and NTRK2 genes were almost absent as they are non‐viable 65–67 …”

“…39 Unsurprisingly, homozygous carriers of mutations were more frequent in endogamic populations, such as Pakistan, Turkey, and Qatar. 63,64 Homozygous carriers of mutations in the SIM1, BDNF, and NTRK2 genes were almost absent as they are non-viable. [65][66][67]…”

Clinical, genetic, and epidemiological survey of Polish children and adolescents with severe obesity: A study protocol of the Polish–German study project on severe early-onset obesity

“…In a US cohort of African American and Latino children with SEOO, three out of eight discovered mutations in MC4R gene were new and not previously reported ( 7 ). A systematic review of the genetics of monogenic obesity in the 22 Arab countries in 13 studies has revealed carried 14 variants in five genes related to monogenic obesity; all of these variants were pathogenic, homozygous, and carried by members of consanguineous families ( 10 ). Unfortunately, there are no data about the prevalence of severe obesity in Polish children as well as about the prevalence of monogenic obesity in Polish SEOO children.…”