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 - Alsters, Suzanne I M
AU - Goldstone, Anthony P
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
AU - Blakemore, Alexandra I F
PY - 2015
Y1 - 2015
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 - Carboxypeptidase H/genetics
KW - DNA Mutational Analysis
KW - Diabetes Mellitus, Type 2/complications
KW - Exome/genetics
KW - Female
KW - Gene Expression Regulation, Enzymologic
KW - Homozygote
KW - Humans
KW - Intellectual Disability/complications
KW - Klinefelter Syndrome/complications
KW - Male
KW - Mutation/genetics
KW - Obesity, Morbid/complications
KW - Pedigree
KW - RNA, Messenger/genetics
KW - Young Adult
U2 - https://doi.org/10.1371/journal.pone.0131417
DO - https://doi.org/10.1371/journal.pone.0131417
M3 - Article
C2 - 26120850
SN - 1932-6203
VL - 10
SP - e0131417
JO - PLOS ONE
JF - PLOS ONE
IS - 6
ER -