We examined 12 monogenic obesity genes in 72 Portuguese individuals with overweight and obesity (class 1 and class 2), some of which with suspected genetic obesity, to identify known or unknown potent Show more
We examined 12 monogenic obesity genes in 72 Portuguese individuals with overweight and obesity (class 1 and class 2), some of which with suspected genetic obesity, to identify known or unknown potential obesity variants. Genomic DNA was analyzed for variants in genes LEP, LEPR, MC4R, POMC, PCSK1, BDNF, NTRK2, SIM1, SH2B1, UCP3, GCG and ADCY3 through next generation sequencing (NGS). The impact of the rare variants was investigated in the ClinVar database and using in silico tools for prediction of pathogenicity. Four potential pathogenic missense variants were detected at the heterozygous state in five individuals: two in the ADCY3 gene, NM₀₀₄₀₃₆.5:c.1153G > A (p.Val385Ile) (rs756783003) and NM₀₀₄₀₃₆.5:c.1222G > A (p.Gly408Arg) (rs201606553), one in gene SH2B1, NM₀₀₁₁₄₅₇₉₅.1:c.127C > A (p.Arg43Ser) (rs547678855), and the fourth in gene POMC NM₀₀₀₉₃₉.4:c.706C > G (p.Arg236Gly) (rs28932472), which was found in two individuals. Moreover, six rare variants near splicing sites were also identified, as well as eight rare synonymous variants. In summary, some potential pathogenic rare missense variants were identified, two of them in ADCY3 gene, the most recently identified gene as having a role in monogenic obesity. Further analysis should be performed to confirm the clinical relevance of these variants. Show less