Endocrine Abstracts

Background: Genetic testing technology has improved considerably in recent years and is now more widely available. In the UK, obesity genetic testing is currently available from the NHS Genomic Medicine Service, or the Rare Obesity Advanced Diagnosis (ROAD) programme. We aimed to enable patients living with obesity the ability to access this genetic testing if they were eligible and interested in exploring this aspect of their care.

Methods: In February 2023 we introduced ROAD genetic testing (a panel of 79 genes and 1 chromosome region) in our regional adult medical obesity clinic. All patients provided written informed consent. Decisions to offer genetic screening were based on: BMI >40 kg/m² (n = 48, 98.0%), early onset in childhood (n = 42, 85.7%), family history (n = 11, 22.4%), features of hyperphagia (n = 6, 12.2%) or developmental delay/learning disability (n = 6, 12.2%).

Results: We performed 60 tests (23 buccal swabs, 37 saliva) in 49 patients (11 repeats, 2 pending). Patients were majority female (n = 31, 63.3%) with mean age 35.3 ± 1.4 yrs, weight 155.9 ± 5.3 kg and BMI 55.3 ± 1.6 kg/m². Pathogenic variants were detected in 8 patients (17.0%), with heterozygosity in PCSK1 (n = 3), POMC (n = 1), MC4R (n = 1) and ch16p11.2 deletion syndrome (n = 3) reported. Variants of unknown significance (VUS) were reported in a further 19 (40.4%) patients. In 20 (42.6%), no pathogenic variants explaining the clinical phenotype were detected.

Conclusion: Aberrations in genes proposed to regulate appetite is common in the medical obesity clinic. Identification may provide patients with an explanation for their weight gain, facilitate testing of family members and enable access to obesity pharmacotherapy in research/treatment pathways. However, VUS detection is likely to be more common with ROAD than the NHS Severe Early-Onset Obesity panel (a smaller panel of 33 genes associated with obesity). Further study on predicting response to obesity treatments based on genotype is needed.