P350: Novel bi-allelic variants in GJC2 associated Pelizaeus-Merzbacker-like disease in three patients at a single center in North India: Case series

Results: Overall, 5,051 individuals were sequenced in Spain (n=1,834), Italy (n=1,291), Trkiye (n=653), Israel (n=501), United Kingdom (n=445), Ireland (n=250), Germany (n=76), and Greece (n=1) of whom 3,040 (60.2%) were aged <18 years.A total of 269 variants were found in 246 unique individuals (4.87%); 88 (1.74%) carried a P/LP/VUS biallelic variant in one of the BBS genes, 41 (0.81%) a P/LP/VUS biallelic variant in AS, 53 (1.05%) a heterozygous variant in TBX3, 67 (1.33%) a heterozygous variant in PHIP, and 20 (0.40%) a heterozygous variant in MAGEL2 (though given maternal imprinting of MAGEL2 gene it is unknown if variant is on paternal allele).For the 161 individuals who were <18 years mean (SD) BMI z-score was 3.5 (1.1) and for the 85 individuals who were 18 BMI was 41.4 (10.6) kg/m 2 .Age of onset of obesity was 4.7 (3.7) years and age of hyperphagia onset 3.8 (2.4) years.Conclusion: Almost 5% of tested individuals carried a biallelic or heterozygous P/LP/VUS variant in 1 of the studied TBX3, PHIP, MAGEL2, AS or BBS genes.By testing patients with early-onset obesity with selected gene panels, or even with Exome Sequencing, a genetic cause might be identified, allowing improved disease awareness and disease management.