TY - JOUR
T1 - Truncating homozygous mutation of Carboxypeptidase E (CPE) in a morbidly obese female with type 2 diabetes mellitus, intellectual disability and hypogonadotrophic hypogonadism
AU - Blakemore, Alexandra I. F.
AU - Goldstone, Anthony P.
AU - Alsters, Suzanne I. M.
AU - Buxton, Jessica L.
AU - Zekavati, Anna
AU - Sosinsky, Alona
AU - Yiorkas, Andrianos M.
AU - Holder, Susan
AU - Klaber, Robert E.
AU - Bridges, Nicola
AU - van Haelst, Mieke M.
AU - le Roux, Carel W.
AU - Walley, Andrew J.
AU - Walters, Robin G.
AU - Mueller, Michael
N1 - Note: This work was supported by Diabetes UK, Biomedical Research Centre, Medical Research Council and the Wellcome Trust.
PY - 2015/6/29
Y1 - 2015/6/29
N2 - 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.
AB - 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.
KW - Biological sciences
UR - https://www.ncbi.nlm.nih.gov/pubmed/26120850
U2 - 10.1371/journal.pone.0131417
DO - 10.1371/journal.pone.0131417
M3 - Article
C2 - 26120850
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e0131417
ER -