A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46,XY patients with disorders of sex development

Wu, Joyce Y., McGown, Ivan N., Lint, Lin, Achermann, John C., Harris, Mark, Cowley, David M., Aftimos, Salim, Neville, Kristen A., Choong, Catherine S. and Cotterill, Andrew M. (2013) A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46,XY patients with disorders of sex development. Clinical Endocrinology, 78 4: 545-550. doi:10.1111/cen.12012

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Author Wu, Joyce Y.
McGown, Ivan N.
Lint, Lin
Achermann, John C.
Harris, Mark
Cowley, David M.
Aftimos, Salim
Neville, Kristen A.
Choong, Catherine S.
Cotterill, Andrew M.
Title A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46,XY patients with disorders of sex development
Formatted title
A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46,XY patients with disorders of sex development
Journal name Clinical Endocrinology   Check publisher's open access policy
ISSN 0300-0664
1365-2265
Publication date 2013-04
Sub-type Article (original research)
DOI 10.1111/cen.12012
Volume 78
Issue 4
Start page 545
End page 550
Total pages 6
Place of publication West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Collection year 2014
Language eng
Formatted abstract
Background
NR5A1 loss-of-function mutations are increasingly found to be the cause of 46,XY disorders of sex development (DSD).
Objective
To determine the presence of NR5A1 mutations in an Australasian cohort of 17 46,XY DSD patients with presumed androgen insensitivity syndrome (AIS) who were negative for androgen receptor gene (AR) mutation.
Design
Exons 2-7 of NR5A1 were PCR amplified and sequenced. Gene expression and cellular localization studies were performed on a novel NR5A1 variant c.74A>G (p.Y25C) identified in this study.
Results
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 in vitro demonstrated reduced transcriptional activation by SF-1 and partially impaired nuclear localization in a proportion of transfected human adrenal NCI-H295R cells.
Conclusion
This is the first reported case of a DSD patient with a NR5A1 mutation and elevated testosterone levels. Our finding supports evaluation of NR5A1 mutations in 46,XY DSD patients with a range of testosterone levels.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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Created: Thu, 04 Apr 2013, 12:40:30 EST by Ms Ramona Hooyer on behalf of Medicine - Mater Hospital