Severe early-onset obesity

Gene: GNB1

I don't know

PMID:38596856 reported three unrelated cases reported with either splicing or truncating variants in GNB1 gene and obesity. Although two of them were reported to start gain weight before 5 years of age, there were no information on their weight or BMI at onset. Hence, we cannot determine the severity of obesity at onset. The third case was reported to have obesity around 9 years of age.

This study also reviewed previously published cases, where two cases were reported with early-onset obesity (<5 years). However, complete information was not available to ascertain the severity.

As per the eligibility criteria on the National Genomic Test Directory (https://www.england.nhs.uk/wp-content/uploads/2018/08/rare-inherited-disease-eligibility-criteria-v8.0.pdf) the patients should have BMI more than 3 standard deviations above the mean, with onset before the age of 5 years. Hence, this gene should be rated amber with the current evidence.

Created: 9 May 2025, 3:18 p.m. | Last Modified: 9 May 2025, 3:19 p.m.

Panel Version: 5.3

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Obesity, HP:0001513

Publications

• 38596856

Green List (high evidence)

75% of cases with truncating variants present with obesity as described in PMID: 38596856
Sources: Literature

Created: 12 Jan 2025, 10:37 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
PMID: 38596856