A Targeted Next Generation Sequencing Panel for Non-syndromic Early Onset Severe Obesity and Identification of Novel Likely -Pathogenic Variants in the MC4R and LEP Genes
To screen for variants in the MC4R and LEP genes in 46 patients with clinical suspicion of non-syndromic early onset severe obesity (NEOSO).
Children with early onset obesity satisfying WHO criteria of obesity were studied. The MC4R and LEP genes were sequenced using a PCR amplicon based NGS on Illumina MiSeq next generation sequencer using an in-house developed protocol.
Of the 46 children tested, four were found to have novel pathogenic/likely-pathogenic variants (one in the MC4R gene and three in the LEP gene). In three out of the 4 families, the presence of the variants was confirmed using standard bidirectional capillary sequencing in the probands.
Four children with novel likely pathogenic variants in the MC4R and LEP genes are reported. Genetic analysis is crucial in children with early onset obesity and should be considered.
KeywordsGenetic obesity Non-syndromic early onset obesity
VK: Concept, patient management and manuscript draft; NP: NGS assay design; NG, PG, RLO: Data collection and manuscript draft; NP, MA, AK, NL: Patient management and manuscript draft. SR, TR, KP, AP, SA, AB: Manuscript draft. KK: Data collection, analysis and manuscript writing. AK is the guarantor for this paper.
Compliance with Ethical Standards
Conflict of Interest