29th Annual Meeting, SLEP, Mérida, Mexico, December 2020: Abstracts

CASTRO SEBASTIÁN; IZQUIERDO AGUSTÍN; SCAGLIA PAULA; ALONSO GUILLERMO; MARTI MARCELO; BRUNELLO FRANCO GINO; BRENZONI LUCIANA; ESNAOLA AZCONTI MARIA; ROPELATO MARIA GABRIELA; REY RODOLFO A; SANSÓ GABRIELA E; BERENSTEIN ARIEL; URRUTIA MARIELA; BERGADÁ IGNACIO; GRINSPON ROMINA P

Hormone research in paediatrics

NLM (Medline)

Año: 2021 vol. 93 p. 1 - 46

The genetic defects of hypogonadotrophic hypogonadism (HH) are known in approximately 30% of cases.Next-generation sequencing (NGS) showed that there may be variants in multiple genes of the same pathway, suggesting an oligogenic aetiology for HH.An 8-year-old boy consulted for cryptorchidism, micro-orchidism and micropenis. At 13 years he was diagnosed with HH by a GnRH test (LH peak: 2 IU/L). Another 14-month-old male consulted for cryptorchidism and micropenis. At 13 years, he was diagnosed with HH by a GnRH test (LH peak: 2.8 IU/L). The remaining hormonal axes were preserved, notably the corticotropic axis. To confirm the aetiology, NGS was performed using the TruSight One capture kit on a NextSeq 500. Filters related to variant frequency ( 10X, GQ> 60) were applied. Variants were classified according to ACMG criteria (P: Pathogenic, VUS: variant of unknown significance). Genomic Evolutionary Rate Profiling (GERP) rejected substitution (RS) score was calculated. In case 1, the previously reported variant PROK2: p.Ile55fs was prioritised (alt/ref alleles: 25/41, ACMG: P, GnomAD: