title: Homozygosity for a novel missense mutation in the leptin receptor gene (P316T) in two Egyptian cousins with severe early onset obesity.
abstract: Congenital deficiency of the leptin receptor is a very rare cause of severe early-onset obesity. To date, only 9 families have been reported in the literature to have mutations in the leptin receptor gene. The clinical features include severe early onset obesity, severe hyperphagia, hypogonadotropic hypogonadism, and T cell and neuroendocrine/metabolic dysfunction. Here we report two cousins with severe early onset obesity and recurrent respiratory tract infections. Their serum leptin levels were elevated but they were within the range predicted by the elevated fat mass in both cousins. Direct sequencing of the entire coding sequence of the leptin receptor gene revealed a novel homozygous missense mutation in exon 6, P316T. The mutation was found in the homozygous form in both cousins and in the heterozygote state in their parents. This mutation was not found in 200 chromosomes from 100 unrelated normal weight control subjects of Egyptian origin using PCR-RFLP analysis. In conclusion, finding this new mutation in the LEPR beside our previous mutation in the LEP gene implies that monogenic obesity syndromes may be common in the Egyptian population owing to the high rates of consanguineous marriages. Further screening of more families for mutations in LEP, LEPR, and MC4 might confirm this assumption.
authors.affiliation: Clinical Genetics Department, National Research Centre, Cairo, Egypt. doctormazen@hotmail.com
authors.forename: I
authors.initials: I
authors.lastname: Mazen
authors.forename: M
authors.initials: M
authors.lastname: El-Gammal
authors.forename: M
authors.initials: M
authors.lastname: Abdel-Hamid
authors.forename: I S
authors.initials: IS
authors.lastname: Farooqi
authors.forename: K
authors.initials: K
authors.lastname: Amr
mesh_terms: D001483:Base Sequence; D016022:Case-Control Studies; D002675:Child, Preschool; D003241:Consanguinity; D004534:Egypt; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D006963:Hyperphagia / Q000235:genetics; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D020125:Mutation, Missense; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D007328:Insulin; C515448:LEPR protein, human; D020738:Leptin; D054411:Receptors, Leptin