A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46, XY patients with disorders of sex development. (12th March 2013)

• Record Type: Journal Article
• Authors: Wu, Joyce Y.; McGown, Ivan N.; Lin, Lin; Achermann, John C.; Harris, Mark; Cowley, David M.; Aftimos, Salim; Neville, Kristen A.; Choong, Catherine S.; Cotterill, Andrew M.
• Is Part Of: Clinical endocrinology. Volume 78:Number 4(2013:Apr.)
• Page Start: 545
• Page End: 550
• Publication Date: 2013-03-12
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1111/cen.12012
• Languages: English
• ISSNs: 0300-0664

Abstract

<abstract abstract-type="main" id="cen12012-abs-0001"> <title>Summary</title> <sec id="cen12012-sec-0001" sec-type="section"> <title>Background</title> <p> <italic>NR5A1</italic> loss‐of‐function mutations are increasingly found to be the cause of 46, XY disorders of sex development (DSD).</p> </sec> <sec id="cen12012-sec-0002" sec-type="section"> <title>Objective</title> <p>To determine the presence of <italic>NR5A1</italic> mutations in an Australasian cohort of 17 46, XY DSD patients with presumed androgen insensitivity syndrome (AIS) who were negative for androgen receptor gene (<italic>AR</italic>) mutation.</p> </sec> <sec id="cen12012-sec-0003" sec-type="section"> <title>Design</title> <p>Exons 2‐7 of <italic>NR5A1</italic> were PCR amplified and sequenced. Gene expression and cellular localization studies were performed on a novel <italic>NR5A1</italic> variant c.74A>G (p.Y25C) identified in this study.</p> </sec> <sec id="cen12012-sec-0004" sec-type="section"> <title>Results</title> <p>We identified one novel mutation, c.74A>G (p.Y25C) in a patient characterized by penoscrotal hypospadias with bifid scrotum. He had elevated testosterone and gonadotropins in early infancy. Functional analysis of p.Y25C <italic>in vitro</italic> demonstrated reduced transcriptional activation by SF‐1 and partially impaired nuclear localization in a proportion of transfected human adrenal NCI‐H295R cells.</p> </sec> <sec id="cen12012-sec-0005" sec-type="section"> <title>Conclusion</title> <p>This is the first reported case of a DSD patient with a <italic>NR5A1</italic> mutation and elevated testosterone levels. Our finding supports evaluation of <italic>NR5A1</italic> mutations in 46, XY DSD patients with a range of testosterone levels.</p> </sec> </abstract>