A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46,XY patients with disorders of sex development
© 2012 Blackwell Publishing Ltd..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2013 |
|---|---|
| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:78 |
|---|---|
| Enthalten in: |
Clinical endocrinology - 78(2013), 4 vom: 07. Apr., Seite 545-50 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wu, Joyce Y [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
3XMK78S47O |
|---|
| Anmerkungen: |
Date Completed 12.09.2013 Date Revised 14.06.2023 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1111/cen.12012 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM22037967X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM22037967X | ||
| 003 | DE-627 | ||
| 005 | 20231224045311.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2013 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/cen.12012 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0734.xml |
| 035 | |a (DE-627)NLM22037967X | ||
| 035 | |a (NLM)22909003 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wu, Joyce Y |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A novel NR5A1 variant in an infant with elevated testosterone from an Australasian cohort of 46,XY patients with disorders of sex development |
| 264 | 1 | |c 2013 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 12.09.2013 | ||
| 500 | |a Date Revised 14.06.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2012 Blackwell Publishing Ltd. | ||
| 520 | |a BACKGROUND: NR5A1 loss-of-function mutations are increasingly found to be the cause of 46,XY disorders of sex development (DSD) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a NR5A1 protein, human |2 NLM | |
| 650 | 7 | |a Steroidogenic Factor 1 |2 NLM | |
| 650 | 7 | |a Testosterone |2 NLM | |
| 650 | 7 | |a 3XMK78S47O |2 NLM | |
| 700 | 1 | |a McGown, Ivan N |e verfasserin |4 aut | |
| 700 | 1 | |a Lin, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Achermann, John C |e verfasserin |4 aut | |
| 700 | 1 | |a Harris, Mark |e verfasserin |4 aut | |
| 700 | 1 | |a Cowley, David M |e verfasserin |4 aut | |
| 700 | 1 | |a Aftimos, Salim |e verfasserin |4 aut | |
| 700 | 1 | |a Neville, Kristen A |e verfasserin |4 aut | |
| 700 | 1 | |a Choong, Catherine S |e verfasserin |4 aut | |
| 700 | 1 | |a Cotterill, Andrew M |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Clinical endocrinology |d 1972 |g 78(2013), 4 vom: 07. Apr., Seite 545-50 |w (DE-627)NLM000089117 |x 1365-2265 |7 nnns |
| 773 | 1 | 8 | |g volume:78 |g year:2013 |g number:4 |g day:07 |g month:04 |g pages:545-50 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/cen.12012 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 78 |j 2013 |e 4 |b 07 |c 04 |h 545-50 | ||