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

Original publication

DOI

10.1371/journal.pone.0131417

Type

Journal article

Journal

PLoS One

Publication Date

2015

Volume

10

Keywords

Carboxypeptidase H, DNA Mutational Analysis, Diabetes Mellitus, Type 2, Exome, Female, Gene Expression Regulation, Enzymologic, Homozygote, Humans, Intellectual Disability, Klinefelter Syndrome, Male, Mutation, Obesity, Morbid, Pedigree, RNA, Messenger, Young Adult