Igarashi, M;
Takasawa, K;
Hakoda, A;
Kanno, J;
Takada, S;
Miyado, M;
Baba, T;
... Fukami, M; + view all
(2016)
Identical NR5A1 Missense Mutations in Two Unrelated 46,XX Individuals with Testicular Tissues.
Human Mutation
, 38
(1)
pp. 39-42.
10.1002/humu.23116.
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Abstract
The role of monogenic mutations in the development of 46,XX testicular/ovotesticular disorders of sex development (DSD) remains speculative. Although mutations in NR5A1 are known to cause 46,XY gonadal dysgenesis and 46,XX ovarian insufficiency, such mutations have not been implicated in testicular development of 46,XX gonads. Here, we identified identical NR5A1 mutations in two unrelated Japanese patients with 46,XX testicular/ovotesticular DSD. The p.Arg92Trp mutation was absent from the clinically normal mothers and from 200 unaffected Japanese individuals. In silico analyses scored p.Arg92Trp as probably pathogenic. In vitro assays demonstrated that compared with wild‐type NR5A1, the mutant protein was less sensitive to NR0B1‐induced suppression on the SOX9 enhancer element. Other sequence variants found in the patients were unlikely to be associated with the phenotype. The results raise the possibility that specific mutations in NR5A1 underlie testicular development in genetic females.
| Type: | Article |
|---|---|
| Title: | Identical NR5A1 Missense Mutations in Two Unrelated 46,XX Individuals with Testicular Tissues |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1002/humu.23116 |
| Publisher version: | https://doi.org/10.1002/humu.23116 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | mutation, NR0B1, NR5A1, SOX9, 46,XX ovotesticular DSD, 46, XX testicular DSD |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10059523 |
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