A novel splice site variant in CYP11A1 in trans with the p.E314K variant in a male patient with congenital adrenal insufficiency

ConclusionCongenital adrenal insufficiency with 46XY sex reversal is a rare disorder that is characterized by dysregulation of steroid hormone synthesis, leading to adrenal and gonadal dysfunction. In this report, we describe a patient with adrenal insufficiency, hypospadias, and skin hyperpigmentation who was found to have a novel c.425+1G>A variant in trans with the p.E314K variant in CYP11A1. We performed structural analyses to examine the effect of the p.E314K variant on protein function and show that it falls in the core of the protein may disrupt cholesterol binding in the active site. In this report, we describe a patient with adrenal insufficiency, hypospadias, and skin hyperpigmentation who was found to have a novel c.425+1G>A variant in trans with the p.E314K variant in CYP11A1. We performed structural analyses to examine the effect of the p.E314K variant on protein function and show that it falls in the core of the protein may disrupt cholesterol binding in the active site.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: Clinical Report Source Type: research

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Marco Vacante1, Antonio Biondi1, Francesco Basile1, Roberto Ciuni1, Salvatore Luca1, Salomone Di Saverio2, Carola Buscemi3, Enzo Saretto Dante Vicari3 and Antonio Maria Borzì3* 1Department of General Surgery and Medical-Surgical Specialties, University of Catania, Catania, Italy 2Cambridge Colorectal Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom 3Department of Clinical and Experimental Medicine, Specialization School in Geriatrics, University of Catania, Catania, Italy There is a high prevalence of hypothyroidism in the elderly population, mainly among women. The mo...
Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
We describe here an updated list of FGD genes and provide a description of relevant mouse models that, despite some being flawed, have been precious allies in the understanding of FGD pathobiology.
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research
Conclusions: The CYP11A1 p.E314K variant impairs P450scc stability and is a possible cause of PAI during childhood. Pathogenic CYP11A1 variants potentially impact both adrenal and gonadal function and males may develop TART. PMID: 30299480 [PubMed - as supplied by publisher]
Source: The Journal of Clinical Endocrinology and Metabolism - Category: Endocrinology Authors: Tags: J Clin Endocrinol Metab Source Type: research
Abstract The discovery of "oestrus-producing" hormones was a major research breakthrough in biochemistry and pharmacology during the early part of the 20th century. The elucidation of the molecular weight and chemical structure of major oxidative metabolites of dehydroepiandrosterone (DHEA) led to the award of the Nobel Prize in 1939 to Adolf Frederick Johann Butenandt and Leopold Ruzicka. Considered a bulk androgen in the circulation, DHEA and its sulfated metabolite DHEA-S can be taken up by most tissues where the sterols are metabolized to active androgenic and estrogenic compounds needed for growth a...
Source: Vitamins and Hormones - Category: Endocrinology Authors: Tags: Vitam Horm Source Type: research
This report of severe early adrenal insufficiency caused by a heterozygous mutation of the CYP11A1 gene clearly demonstrates that SCC deficiency may be inherited as an autosomal dominant trait in humans. PMID: 29995203 [PubMed - as supplied by publisher]
Source: Hormones - Category: Endocrinology Tags: Hormones (Athens) Source Type: research
Authors: Okuma H, Hashimoto K, Ohashi T, Mihara M, Minami I, Izumiyama H, Sasaki S, Inoshita N, Nishioka H, Yamada S, Yoshimoto T Abstract A 29-year-old man was referred to our department due to adrenal insufficiency with the inappropriate secretion of TSH (SITSH). Magnetic resonance imaging revealed a pituitary tumor. A weak TSH response in the TRH test, elevated sex hormone binding globulin (SHBG) levels, and the absence of a family medical history of SITSH or TRβ gene mutations supported the diagnosis of TSH-secreting pituitary adenoma (TSHoma). However, complete TSH suppression and a blunted cholesterol re...
Source: Endocrine Journal - Category: Endocrinology Tags: Endocr J Source Type: research
Comprehensive Endocrine-Metabolic Evaluation of Patients with Alström Syndrome Compared to BMI-Matched Controls. J Clin Endocrinol Metab. 2018 Apr 27;: Authors: Han JC, Reyes-Capo DP, Liu CY, Reynolds JC, Turkbey E, Turkbey IB, Bryant J, Marshall JD, Naggert JK, Gahl WA, Yanovski JA, Gunay-Aygun M Abstract Background: Alström syndrome (AS), a monogenic form of obesity, is caused by recessive mutations in the centrosome- and basal body-associated gene, ALMS1. AS is characterized by retinal dystrophy, sensory hearing loss, cardiomyopathy, childhood obesity, and metabolic derangements. Obj...
Source: The Journal of Clinical Endocrinology and Metabolism - Category: Endocrinology Authors: Tags: J Clin Endocrinol Metab Source Type: research
Conclusion: We report the first case of the combination of 2 rare genetic disorders, Angelman syndrome, and P450scc deficiency. After 20 years of diagnostic efforts, significant advances in genetic diagnostic technology allowed us to determine that these 2 disorders originate from a unified genetic etiology, segmental UPD unmasking a novel recessive mutation inCYP11A1.Horm Res Paediatr
Source: Hormone Research in Paediatrics - Category: Endocrinology Source Type: research
Aim: High density lipoprotein (HDL) cholesterol is not decreased in hypercortisolism despite high triglycerides, which may be ascribed to effects on the cholesteryl ester transfer protein (CETP) pathway. We explored if CETP mRNA expression is modulated by glucocorticoid treatment in vitro. Effects of doubling the hydrocortisone (HCT) replacement dose on plasma CETP activity and HDL characteristics were tested in patients with secondary adrenal insufficiency.
Source: Atherosclerosis - Category: Cardiology Authors: Source Type: research
ConclusionTo our knowledge this is the second case of classic lipoid congenital adrenal hyperplasia reported in the Italian population. STAR mutations resulting in lipoid congenital adrenal hyperplasia should be considered all over the world in the differential diagnosis of newborn babies and infants with primary adrenal insufficiency.
Source: Italian Journal of Pediatrics - Category: Pediatrics Source Type: research
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