Severe early-onset obesity

Gene: CPE

The rating of this gene has been updated to GREEN following NHS Genomic Medicine Service approval.

Created: 31 Jan 2023, 2:31 p.m. | Last Modified: 31 Jan 2023, 2:31 p.m.

Panel Version: 3.3

Green List (high evidence)

Comment on list classification: There are now sufficient unrelated families (5) reported in literature presenting a relevant phenotype associated with variants in this gene to rate as Green at the next GMS panel update.

Created: 28 Sep 2021, 3:05 p.m. | Last Modified: 28 Sep 2021, 3:05 p.m.

Panel Version: 2.43

Durmaz et al. 2021 (PMID: 32936766) identified the second family with 3 affected sibs with obesity, intellectual disability and hypogonadotropic hypogonadism, and a homozygous nonsense c.405C>A (p.Y135*) variant in CPE.

Bosch et al. 2021 (PMID: 34383079) reported on 4 individuals from 3 additional families harbouring 2 different homozygous truncating variants in this gene. Clinical presentation was prominent for obesity and intellectual disability. Hypogonadotropic hypogonadism was confirmed in one individual and was suspected but not tested for in another two subjects.

Created: 28 Sep 2021, 3:04 p.m. | Last Modified: 28 Sep 2021, 3:04 p.m.

Panel Version: 2.41

Comment on phenotypes: CPE is now associated with a relevant phenotype in OMIM - Intellectual developmental disorder and hypogonadotropic hypogonadism, MIM# 619326

Created: 22 Jun 2021, 2:42 p.m. | Last Modified: 22 Jun 2021, 2:42 p.m.

Panel Version: 2.39

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual developmental disorder and hypogonadotropic hypogonadism, OMIM:619326

Publications

• 26120850
• 32936766
• 34383079

I don't know

CPE is not associated with any phenotype on OMIM or Gene2Phenotype. PMID: 26120850 reported on a consanguineous Sudanese family with Mendelian pattern of obesity. The proband had childhood onset obesity, ID, T2DM and hypogonadotrophic hypogonadism and was homozygous for truncating mutation. There were 4 other family members who were heterozygous for this variant who were mildly obese but did not have ID or hypogonadotrophic hypogonadism. The proband's phenotype resembles Cpe knockout mouse and fat/fat mouse models. However, there is currently not enough evidence to support a gene-disease association.

Created: 15 Aug 2019, 2:02 p.m. | Last Modified: 15 Aug 2019, 2:02 p.m.

Panel Version: 1.22

Publications

• 26120850

Green List (high evidence)

Variants in this GENE are reported as part of current diagnostic practice

Comment on list classification: Candidate gene. Gene added by expert reviewer. CPE knockout mice become obese within 10-14 weeks, and develop endocrinological and behavioral deficits (PMID: 15358678, 15870393). Several publications linking variants in the gene to atherosclerosis. Gene not associated with a disease/phenotype in OMIM, Gene2Phenotype, Orphanet or DECIPHER. Obesity HPO term not associated with CPE. No single variants in ClinVar reported in CPE...only structural variants that include this gene and others.

Created: 16 Oct 2016, 10:19 a.m.