Identification of novel pathogenic variants in the GNAS gene in children with morbid obesity and pseudohypoparathyroidism

Pseudohypoparathyroidism (PHP) is a clinically heterogeneous group of rare inherited bone diseases characterized by resistance of target organs to the action of parathormone (PTH) as result of an epi/genetic disorder.This article describes patients with the phenotype of pseudohypoparathyroidism type 1a in whom two previously undescribed variants in the GNAS gene were identified: NM_000516.7(GNAS):c.586-18_591del, which captures intron 7, exon 8 acceptor splice site and exon 8 splice site resulting in a 24 nucleotide deletion, and NM_000516.7(GNAS):c.201del p.Phe68LeufsTer32 resulting in a reading frame shift and a premature termination codon in two unrelated children with progressive weight gain from birth. According to the pathogenicity evaluation criteria, both variants are categorized as likely pathogenic variants