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RESEARCH PRODUCT

Genetic screening for MC4R gene identifies three novel mutations associated with severe familiar obesity in a cohort of Spanish individuals

Amor García BanacloyDavid AlbuquerqueClara Vidal GarciaRaquel Rodríguez-lópezGoitzane Marcaida BenitoMarcos Bruna EstebanCarola Guzmán LujánCarlos Sánchez JuanFátima Gimeno-ferrer

subject

AdultMale0301 basic medicineAdolescentObesity phenotypeIn silicoDNA Mutational AnalysisMutation MissenseOverweightBiologymedicine.disease_causePolymorphism Single NucleotideCohort StudiesYoung Adult03 medical and health sciences0302 clinical medicineGeneticsmedicineHumansGenetic Predisposition to DiseaseGenetic TestingGeneGenetic Association StudiesGeneticsMutationPromoterGeneral MedicineMiddle Agedmedicine.diseaseObesityObesity MorbidPedigree030104 developmental biologySpainCase-Control Studies030220 oncology & carcinogenesisCohortReceptor Melanocortin Type 4Femalemedicine.symptom

description

Abstract MC4R gene is a hypothalamic satiety control mediator in which mutations cause a monogenic form of obesity. The aim of this study was to perform a genetic screening to identify variations in the entire region of MC4R gene. A total of 236 unrelated and severely obese patients (BMI ≥ 40 kg/m2) with Spanish ancestry and severe overweight familiar history have been enrolled into the study. Seven MC4R gene variants were identified in the heterozygous state in 21 patients. Coding variants p.Thr101Ile and p.Ala259Asp are new and variants p.Ser30Phe, p.Val103Ile and p.Ile251Leu were previously described. Two variants have been also observed in the promoter region of the MC4R gene; the c.-24G>A mutation, described for the first time, and the known c.-178A>C variant. Both in silico and family segregation analysis confirm the correlation between novel identified mutations in MC4R gene and obesity development. The correlation between the four variants (c.-24G>A, p.Thr101Ile, p.Ala259Asp and p.Ser30Phe) and the obesity phenotype, therefore, allows the conclusion that all of the four mutations cause a monogenic form of obesity.

yearjournalcountryeditionlanguage
2019-07-01Gene
https://doi.org/10.1016/j.gene.2019.04.018