Anita Morandi, Elena Fornari, Massimiliano Corradi, Giuseppina Rosaria Umano, Francesca Olivieri, Claudia Piona, Alice Maguolo, Carola Panzeri, Federica Emiliani, Grazia Cirillo, Paolo Cavarzere, Emanuele Miraglia Del Giudice, Claudio Maffeis
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引用次数: 0
Abstract
Background
The diagnosis of monogenic obesity is burdened by frequent variants of uncertain significance (VUS). We describe our real-life approach of variant reassessment over time and we assess whether inconclusive variants are decreasing in monogenic obesity.
Methods
We tested for monogenic obesity (genes: LEPR, POMC, ADCY3, PCSK1, CARTPT, SIM1, MRAP2, LEP, NTRK2, BDNF, KSR2, MAGEL2, SH2B1, MC4R, MC3R) in 101 children/adolescents (11.7 [7.3–13.7] years, 3.6 [3.3–4.0] z-BMI) in Verona and 183 (11.3 [8.4–12.2] years, 3.2 [2.7–3.9] z-BMI) in Naples from January 2020 to February 2023. In March–July 2024 we reassessed the baseline variants by updated software interpretation and literature renavigation.
Results
We initially found 20 VUS, 4 Likely Pathogenic (LP), 5 Likely Benign (LB) and 1 benign variant in 33 individuals. At follow-up, 6 VUS were reclassified as benign/LB, one LP as pathogenic and 3 LB as benign. Overall, 10/30 variants (6/18 in Verona, 3/11 in Naples and a variant found in both centres) were reclassified, leading to a less uncertain report for 13 of 33 variant-carrying patients. Monogenic obesity was diagnosed in 3 probands in Verona and 4 in Naples, carrying variants at MC4R or NTRK2.
Conclusion
Our variant reassessment was effective to improve classification certainty for the 39% of patients and suggested that the molecular diagnosis of monogenic obesity is becoming more accurate over time.
期刊介绍:
Pediatric Obesity is a peer-reviewed, monthly journal devoted to research into obesity during childhood and adolescence. The topic is currently at the centre of intense interest in the scientific community, and is of increasing concern to health policy-makers and the public at large.
Pediatric Obesity has established itself as the leading journal for high quality papers in this field, including, but not limited to, the following:
Genetic, molecular, biochemical and physiological aspects of obesity – basic, applied and clinical studies relating to mechanisms of the development of obesity throughout the life course and the consequent effects of obesity on health outcomes
Metabolic consequences of child and adolescent obesity
Epidemiological and population-based studies of child and adolescent overweight and obesity
Measurement and diagnostic issues in assessing child and adolescent adiposity, physical activity and nutrition
Clinical management of children and adolescents with obesity including studies of treatment and prevention
Co-morbidities linked to child and adolescent obesity – mechanisms, assessment, and treatment
Life-cycle factors eg familial, intrauterine and developmental aspects of child and adolescent obesity
Nutrition security and the "double burden" of obesity and malnutrition
Health promotion strategies around the issues of obesity, nutrition and physical activity in children and adolescents
Community and public health measures to prevent overweight and obesity in children and adolescents.