Truncating Homozygous Mutation of Carboxypeptidase E (CPE) in a Morbidly Obese Female with Type 2 Diabetes Mellitus, Intellectual Disability and Hypogonadotrophic Hypogonadism

摘要: Carboxypeptidase E is a peptide processing enzyme, involved in cleaving numerous precursors, including neuropeptides and hormones appetite control glucose metabolism. Exome sequencing of morbidly obese female from consanguineous family revealed homozygosity for truncating mutation the CPE gene (c.76_98del; p.E26RfsX68). Analysis detected no expression whole blood-derived RNA proband, consistent with nonsense-mediated decay. The morbid obesity, intellectual disability, abnormal homeostasis hypogonadotrophic hypogonadism seen this individual recapitulates phenotypes previously described fat/fat Cpe knockout mouse models, evidencing importance peptide/hormone-processing enzyme regulating body weight, metabolism, brain reproductive function humans.