A novel pathogenic variant in MRAP2 in an obese patient with successful outcome of bariatric surgery.
Blandine Gatta CherifiAlexandre LaboyeCaroline GronnierMaud Monsaingeon-HenrySarah MeulebrouckMorgane BaronFrançoise BertinEmilie PupierSophie CambosChristine PoitouJohanne Le Beyec-Le BihanAmélie BonnefondPublished in: European journal of endocrinology (2023)
Mutations in genes encoding proteins located in the leptin/melanocortin pathway have been identified in the rare cases of genetic obesities. Heterozygous variants of MRAP2, encoding a G coupled-protein receptor accessory protein implicated in energy control notably via the melanocortin-4 receptor, have been recently identified. A 24-year-old patient with early-onset severe obesity (body mass index [BMI]: 64 kg/m2) associated with hypertension, respiratory complications, nonalcoholic fatty liver disease, and type 2 diabetes was referred to our department. Sleeve gastrectomy was successful. A new heterozygous variant in MRAP2 (NM_138409.4: c.154G>C/p.G52R) variant was identified in the patient DNA. Functional assessment confirmed that this new variant was pathogenic. We report a new pathogenic loss-of-function mutation in MRAP2 in a patient suffering from a severe multicomplicated obesity. This confirms the metabolic phenotype in patients with this monogenic form of obesity. Longer follow-up will be necessary. Our finding will allow a personalized medicine.
Keyphrases
- early onset
- type diabetes
- weight loss
- body mass index
- metabolic syndrome
- bariatric surgery
- insulin resistance
- weight gain
- case report
- late onset
- adipose tissue
- blood pressure
- high fat diet induced
- genome wide
- physical activity
- copy number
- binding protein
- glycemic control
- risk factors
- dna methylation
- skeletal muscle
- cell free
- protein protein
- clinical evaluation
- bioinformatics analysis