Truncating Homozygous Mutation of Carboxypeptidase E (CPE) in a Morbidly Obese Female with Type 2 Diabetes Mellitus, Intellectual Disability and Hypogonadotrophic Hypogonadism
| Autor: | Alsters, Suzanne I. M., Goldstone, Anthony P., 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. |
|---|---|
| Přispěvatelé: | Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Fat/fat mice DNA Mutational Analysis lcsh:Medicine Case Reports Gene Expression Regulation Enzymologic E gene Young Adult Klinefelter Syndrome Early-onset obesity Intellectual Disability Melanocyte-stimulating hormone Journal Article Humans Missense mutation Exome RNA Messenger lcsh:Science health care economics and organizations Research Support Non-U.S. Gov't lcsh:R Homozygote Carboxypeptidase H Obesity Morbid Pedigree Pituitary Diabetes Mellitus Type 2 Mutation lcsh:Q Female biological Research Article |
| Zdroj: | PLoS ONE Alsters, S I M, Goldstone, A P, Buxton, J L, Zekavati, A, Sosinsky, A, Yiorkas, A M, Holder, S, Klaber, R E, Bridges, N, van Haelst, M M, le Roux, C W, Walley, A J, Walters, R G, Mueller, M & Blakemore, A I F 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, vol. 10, no. 6, pp. e0131417 . https://doi.org/10.1371/journal.pone.0131417 PLoS ONE [E], 10(6). Public Library of Science PLoS ONE, Vol 10, Iss 6, p e0131417 (2015) PLoS ONE, 10(6). Public Library of Science |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0131417 |
| Popis: | 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. The Section of Investigative Medicine is funded by grants from the Medical Research Council, Biotechnology and Biological Sciences Research Council (BBSRC), National Institute for Health Research (NIHR), an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7- HEALTH- 2009- 241592 EuroCHIP grant, and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. This work was also funded by a project grant from Diabetes UK to AB and RW, and Biomedical Research Centre awards to AB, RW, MVH and CLR. Authors AB and AG are each also funded by the UK Medical Research Council. JB is also funded by the Wellcome Trust. The Imperial Genomics Facility is funded by the NIHR Imperial BRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|