Genetic diagnosis of congenital hypopituitarism by Molecular Inversion Probes Sequencing: novel pathogenic variants

Abstract

Congenital hypopituitarism (CH) is a life-long and threatening disease, associated with an abnormal pituitary development. CH is highly variable comprising a spectrum of disorders that range from isolated growth hormone deficiency (IGHD) to combined pituitary hormone deficiency (CPHD). Mutations in at least 30 genes have been implicated in CH, but atpresent, precise diagnosis remains a challenge. In the present study, we report variants found in pediatric patients with CPHD (n=116) or IGHD (n=55) from Argentina using the molecular inversion probes sequencing (MIPS) method and our own custom designed gene panel. We identified pathogenic, likely pathogenic or variants with uncertain significance but predicated to be damaging for at least 3 independent software in about 23% of the cases.