Variant reclassification over time decreases the level of diagnostic uncertainty in monogenic obesity: Experience from two centres
Authors' 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.
Study context
- Population
- Children/adolescents tested for monogenic obesity (LEPR, POMC, ADCY3, PCSK1, CARTPT, SIM1, MRAP2, LEP, NTRK2, BDNF, KSR2, MAGEL2, SH2B1, MC4R, MC3R) in Verona (n=101; 11.7 [7.3–13.7] years, z-BMI 3.6 [3.3–4.0]) and Naples (n=183; 11.3 [8.4–12.2] years, z-BMI 3.2 [2.7–3.9]), January 2020 to February 2023; variants reassessed March-July 202433 variant carriers
- Participants
- 101 vs 183
- Exposure
- Verona vs Naples
- Veronan = 101
- Naplesn = 183
- Outcome
- Reclassification of baseline variants by updated software interpretation and literature renavigation
- Follow-up
- March-July 2024
Methodological detailstwo-centre, variant reassessment over time
- Two-centre
- Variant reassessment over time
Main finding
As reported in the abstract
Variant reclassification · follow-up (March-July 2024)
Verona
6 of 18
events
Naples
3 of 11
events
- Variants reclassified overall (incl. one variant found in both centres)
- 10/30
- Variants of uncertain significance (VUS) reclassified as benign/Likely Benign (LB)
- 6
- Likely Pathogenic (LP) reclassified as pathogenic
- 1
- LB reclassified as benign
- 3
- Variant-carrying patients with a less uncertain report
- 13 of 33
Observational data: associations, not effects.
Further findings
Events
| Outcome | Verona | Naples |
|---|---|---|
| Monogenic obesity diagnosed (variants at MC4R or NTRK2) | 3 | 4 |
Original publication
Variant reclassification over time decreases the level of diagnostic uncertainty in monogenic obesity: Experience from two centres. Pediatr Obes. Published 27 October 2024. doi:10.
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