RF17 | PMON23 Argentinian multicentric genetic study of pituitary hormonal deficiencies using a custom panel based on single molecule molecular inversion probes

Abstract Hypopituitarism with deficiency of one or more pituitary hormones (combined hormone CPHD) can vary in severity and age at presentation. Additionally, the abnormalities may evolve time necessitating frequent evaluation. These hormonal deficits also be present as part a syndrome, patients showing extrapituitary such eye forebrain malformations. Over past decade, there has been an explosion knowledge genetic cascade that orchestrates hypothalamic development. Several transcription factors signaling molecules are critical for cell differentiation proliferation very early stage gestation. However, genes remain to identified order provide definitive aetiology. We studied 95 children congenital hypopituitarism from seven pediatric hospitals Argentina. Children non-endocrine, non-familial idiopathic short stature served control group (n=100). A custom exon capture panel based on single-molecule molecular inversion probes sequencing (MIPS) was performed probands parents. This tests 104 genes: including selection reported candidate chosen our development mice PROP1 interacting proteins. found least 1 variant 50 probands. The prevalence known variants factor PIT1 (frequently mutated low cohort. significant number disease-causing were LHX3, LHX4, GLI2 OTX2. An important advance study is identification pathogenic recently discovered novel genes. heterozygous Roundabout (ROBO) receptor homolog gene: ROBO1;p.Arg1504* patient CPHD septo-optic dysplasia (SOD); two Steroid Receptor SRA1: p. Ile179Thr p.Val110delinsArgLeu hypogonadism hypogonadotropic missense Semaphorin 3A SEMA3A: p.Val588Leu case aortic coarctation. Our findings support evidence etiology highly heterogeneous infrequently monogenic full penetrance, underlying complex pathogenesis. Presentation: Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m., Monday, 13, 12:30 2:30