Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 94, Issue 10, Pages 3865-3871Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2009-0467
Keywords
-
Categories
Funding
- Wellcome Trust [076430]
- Medical Research Council United Kingdom [G116/172, G0801265]
- Orchid Appeal
- European Commission
- MRC [G0900567, G116/172, G0801265] Funding Source: UKRI
- Medical Research Council [G0900567, G0801265, G116/172] Funding Source: researchfish
Ask authors/readers for more resources
Context: Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder resulting from resistance to the action of ACTH on the adrenal cortex. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia and/or overwhelming infection. Mutations of the ACTH receptor (MC2R) and the melanocortin 2 receptor accessory protein (MRAP), FGD types 1 and 2 respectively, account for approximately 45% of cases. Objective: A locus on chromosome 8 has previously been linked to the disease in three families, but no underlying gene defect has to date been identified. Design: The study design comprised single-nucleotide polymorphism genotyping and mutation detection. Setting: The study was conducted at secondary and tertiary referral centers. Patients: Eighty probands from families referred for investigation of the genetic cause of FGD participated in the study. Interventions: There were no interventions. Results: Analysis by single-nucleotide polymorphism array of the genotype of one individual with FGD previously linked to chromosome 8 revealed a large region of homozygosity encompassing the steroidogenic acute regulatory protein gene, STAR. We identified homozygous STAR mutations in this patient and his affected siblings. Screening of our total FGD patient cohort revealed homozygous STAR mutations in a further nine individuals from four other families. Conclusions: Mutations in STAR usually cause lipoid congenital adrenal hyperplasia, a disorder characterized by both gonadal and adrenal steroid deficiency. Our results demonstrate that certain mutations in STAR (R192C and the previously reported R188C) can present with a phenotype indistinguishable from that seen in FGD. (J Clin Endocrinol Metab 94: 3865-3871, 2009)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available