IDENTIFICATION OF 2 NOVEL MISSENSE MUTATIONS IN THE HUMAN OB GENE

OBJECTIVE: To clone the human OB gene and to investigate if mutations in the OB gene are related to juvenile onset obesity in Caucasians. DE SIGN: Case-cohort study with mutational scanning of the OB gene in an obese cohort and in a population sample of young Caucasians. SUBJECTS: An obese cohort of 156 subjects with juvenile onset obesity and a pop ulation sample of 380 healthy young Caucasians. MEASUREMENTS: Various anthropometric and biochemical measures of obesity and insulin sensiti vity and single strand conformation polymorphism scanning and nucleoti de sequencing. RESULTS: Analysis of the coding region of the OB gene i n the 536 participants revealed that one obese subject was heterozygou s for a mutation at codon Phe17Leu and one normal weight subject was h eterozygous for a mutation at codon Val110Met. The phenotypes of the c arriers were not different from matched non-mutation carrying subjects . CONCLUSIONS: Mutations exist in the OB gene among obese as well as l ean subjects although they are rare. However, it is unlikely that muta tions in the coding region of the OB gene are a common cause of juveni le onset obesity among Caucasians.