IMPE Abstracts

Mutations in the GH1 gene cause isolated growth hormone deficiency (IGHD) by affecting the production, secretion, and stability of growth hormone as well as its binding to GHR. Genetic mutations resulting from splicing errors are known to increase the production of a small 17.5 kD isoform of human growth hormone. The smaller isoform of GH1 is inactive and is linked to IGHD. We found that cells transfected with the mutated GH gene that produced the short 17.5 kD version of GH, ...

Background: Steroidogenic factor 1 (SF-1/NR5A1) is a nuclear receptor that regulates sex development, steroidogenesis and reproduction. Genetic variants in SF-1/NR5A1 are common among differences of sex development (DSD) and associate with a wide range of phenotypes, but their pathogenic mechanisms remain unclear. We aimed at characterizing novel missense, likely disease-causing SF-1/NR5A1 variants in a large cohort of DSD individual...

Background: Variants in Steroidogenic Factor 1 (SF-1/NR5A1) lead to a broad spectrum of phenotypes including differences of sex development (DSD). Individuals with DSD are born more often small for gestational age and are smaller than the general population, but mechanisms remain unclear. In this study we assessed if SF-1/NR5A1 variants may play a role in growth impairment and whether auxological parameters correlate with the degree of DSD in an inter...

Background and Aim: The SF-1/NR5A1 variant c.437G>C/p.Gly146Ala is common among individuals with disorders/differences of sex development (DSD). It has been considered a polymorphism due to its high allele frequency in the control population (23.5%, gnomAD) and its lack of negative effect in cell-based studies. However, its possible role as a disease modifier is still unclear given that oligogenic inheritance has been described in patients with SF1...