Truncating Homozygous Mutation of Carboxypeptidase E (CPE) in a Morbidly Obese Female with Type 2 Diabetes Mellitus, Intellectual Disability and Hypogonadotrophic Hypogonadism

被引：60

作者：

Alsters, Suzanne I. M. ^{[1
]}

Goldstone, Anthony P. ^{[2
,3
,4
]}

Buxton, Jessica L. ^{[1
,5
]}

Zekavati, Anna ^{[6
]}

Sosinsky, Alona ^{[6
]}

Yiorkas, Andrianos M. ^{[1
]}

Holder, Susan ^{[7
]}

Klaber, Robert E. ^{[8
]}

Bridges, Nicola ^{[9
]}

van Haelst, Mieke M. ^{[10
]}

le Roux, Carel W. ^{[1
,11
]}

Walley, Andrew J. ^{[12
]}

Walters, Robin G. ^{[13
,14
]}

Mueller, Michael ^{[6
]}

Blakemore, Alexandra I. F. ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Diabet Endocrinol & Metab, Sect Invest Med, London, England

[2] Hammersmith Hosp, Imperial Coll Healthcare NHS Trust, Imperial Ctr Endocrinol, London, England

[3] Univ London Imperial Coll Sci Technol & Med, Ctr Neuropsychopharmacol & Computat, Cognit & Clin Neuroimaging Lab, Hammersmith Hosp,Dept Med,Div Brain Sci, London, England

[4] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, MRC, Metab & Mol Imaging Grp,Clin Sci Ctr, London, England

[5] UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England

[6] Univ London Imperial Coll Sci Technol & Med, Fac Med, NIHR Imperial BRC Genom Facil, London, England

[7] Northwick Pk Hosp & Clin Res Ctr, North West London Hosp NHS Trust, Kennedy Galton Ctr, NW Thames Reg Genet Serv, Harrow HA1 3UJ, Middx, England

[8] St Marys Hosp, Dept Paediat, Imperial Coll Healthcare NHS Trust, London, England

[9] Chelsea & Westminster Hosp, Dept Paediat Endocrinol, London, England

[10] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Med Genet, Utrecht, Netherlands

[11] Univ Coll Dublin, Sch Med & Med Sci, Conway Inst, Diabet Complicat Res Ctr, Dublin 2, Ireland

[12] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England

[13] Univ Oxford, Clin Trial Serv Unit, Nuffield Dept Populat Hlth, Oxford, England

[14] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Oxford, England

来源：

PLOS ONE | 2015年 / 10卷 / 06期

基金：

英国惠康基金; 英国医学研究理事会; 英国生物技术与生命科学研究理事会;

关键词：

EARLY-ONSET OBESITY; MELANOCYTE-STIMULATING HORMONE; MISSENSE MUTATION; FAT/FAT MICE; GENE; BRAIN; CONVERTASE; BEHAVIORS; PITUITARY;

D O I：

10.1371/journal.pone.0131417

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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