Severe early-onset obesity

Gene: ADCY3

Green List (high evidence)

PMID:29311636 - Founder canonical splice variant (c.2433-1G>A) reported in Greenlandic populations demonstrate higher risk of obesity and type 2 diabetes in homozygous individuals.

PMID:29311637 - Four children from three consanguineous Pakistani families were reported with severe early-onset obesity and identified with three different homozygous variants in ADCY3 gene. In addition, an obese boy of European-American descent was identified with heterozygous ADCY3 variants.

PMID:35026759 - Two additional heterozygous variants (c.1658C>T/ p.Ala553Val & c.489C>G/ p.His163Gln) were identified in six Qatari individuals with obesity. However, the authors of this publication struggle to draw a conclusion on the impact of the dominant effect of the variants due to the genetic and biological overlap between monogenic and the common form of obesity.

The phenotypes of biallelic variants appear severe and early-onset. The age of patients with monoallelic variants ranged from 28 and 57 and its was not clear whether the patients had either monogenic or common form of obesity. Hence, the MOI should be set as "BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal".

Created: 1 Sep 2023, 9:36 a.m. | Last Modified: 1 Sep 2023, 9:36 a.m.

Panel Version: 1.9

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
{Obesity, susceptibility to, BMIQ19}, OMIM:617885

Publications

• 29311636
• 29311637
• 35026759

I don't know

PMID: 29311636 - founder canonical splice variant (c.2433-1G>A) in Greenlandic populations demonstrate higher risk of obesity, type 2 diabetes in homozygous individuals PMID: 29311637 - 4 unrelated families with severe early onset obesity, three with homozygous variants.
Sources: Expert Review

Created: 28 Mar 2022, 7:25 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
{Obesity, susceptibility to, BMIQ19} MIM#617885

Publications

• 11055432
• 29311636
• 29311637