A novel pathogenic variant in MRAP2 in an obese patient with successful outcome of bariatric surgery

Area of Science:

• Genetics
• Endocrinology
• Metabolic Disorders

Background:

• Rare genetic mutations in the leptin/melanocortin pathway are linked to obesity.
• MRAP2, a gene encoding a G protein-coupled receptor accessory protein, plays a role in energy homeostasis, particularly through the melanocortin-4 receptor.

Observation:

• A 24-year-old patient presented with severe early-onset obesity (BMI 64 kg/m2), hypertension, respiratory issues, nonalcoholic fatty liver disease, and type 2 diabetes.
• Genetic analysis revealed a new heterozygous variant (NM_138409.4: c.154G>C/p.G52R) in the MRAP2 gene.
• Functional studies confirmed the pathogenic nature of this MRAP2 variant, indicating a loss-of-function mutation.

Findings:

• The study identified a novel pathogenic loss-of-function mutation in the MRAP2 gene in a patient with severe, multi-complicated obesity.
• This finding reinforces the association between MRAP2 gene mutations and a specific monogenic form of obesity.
• The identified variant was confirmed to be pathogenic through functional assessment.

Implications:

• This discovery confirms the metabolic phenotype associated with MRAP2 mutations, contributing to the understanding of monogenic obesity.
• The identification of this pathogenic variant allows for potential personalized medicine strategies for affected individuals.
• Further long-term follow-up is warranted to fully understand the clinical trajectory and management of patients with MRAP2-related obesity.