IMPE Abstracts

Introduction: Over-production of androgens is linked to prostate cancer (PCa) in men and polycystic ovary syndrome (PCOS) in women. CYP17A1 produces dehydroepiandrosterone (DHEA), the precursor for androgens, via its 17,20 lyase activity. CYP17A1 lyase activity is regulated by the amount of P450 reductase for electron transfer; the presence of cytochrome b5; and protein phosphorylation. High androgen levels were linked to the phosphorylation of CYP17A1 protein...

Introduction: Cytochrome P450 oxidoreductase (POR) acts as a redox partner of all microsomal cytochrome P450s which metabolize drugs and steroid hormones. Mutations in POR cause congenital adrenal hyperplasia (CAH) and/or disorders of sexual development (DSD) due to defective biosynthesis of steroid hormones in the adrenal and gonads, and affect the hepatic metabolism of drugs. The variant V631I was previously identified only in healthy heterozygous carriers. ...

Background: The adrenocorticotropic hormone (ACTH) is a 39 amino acid polypeptide secreted by the anterior pituitary and regulates cortisol secretion from the adrenal cortex. Cortisol has a negative feedback mechanism and regulates the biosynthesis and secretion of ACTH. Excess of ACTH is associated with a wide range of diseases including congenital adrenal hyperplasia (CAH). Classic CAH due to the 21-hydroxylase (CYP21A2) deficiency causes a reduction or loss...

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, ...

Introduction: GH1 was the first gene associated with isolated GH deficiency (IGHD) due to a gene deletion described in 1981. Subsequently, frameshift, homozygous missense and nonsense allelic variants, and splice site allelic variants causing GHD were reported.Aim: Use whole exome sequencing (WES) in the search of variants in known genes and also new genes associated to IGHD and determine the effect of variants....