Truncating homozygous mutation of Carboxypeptidase E (CPE) in a morbidly obese female with type 2 diabetes mellitus, intellectual disability and hypogonadotrophic hypogonadism

Goldstone, Anthony P., Alsters, Suzanne I. M., Buxton, Jessica L., Zekavati, Anna, Sosinsky, Alona, Yiorkas, Andrianos M., Holder, Susan, Klaber, Robert E., Bridges, Nicola, van Haelst, Mieke M., le Roux, Carel W., Walley, Andrew J., Walters, Robin G., Mueller, Michael, Blakemore, Alexandra I. F., and (2015) Truncating homozygous mutation of Carboxypeptidase E (CPE) in a morbidly obese female with type 2 diabetes mellitus, intellectual disability and hypogonadotrophic hypogonadism. PLoS ONE, 10(6), e0131417. ISSN (online) 1932-6203

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Abstract

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.

Item Type: Article
Additional Information: This work was supported by Diabetes UK, Biomedical Research Centre, Medical Research Council and the Wellcome Trust.
Research Area: Biological sciences
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing (until 2017) > School of Life Sciences
Faculty of Science, Engineering and Computing (until 2017) > School of Pharmacy and Chemistry
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Depositing User: Jessica Buxton
Date Deposited: 11 Dec 2017 12:12
Last Modified: 06 Sep 2019 09:42
DOI: https://doi.org/10.1371/journal.pone.0131417
URI: http://eprints.kingston.ac.uk/id/eprint/40218

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