Case report of whole genome sequencing in the XY female: identification of a novel SRY mutation and revision of a misdiagnosis of androgen insensitivity syndrome

Files

hdl_103898.pdf (2.85 MB)
  (Published version)

Date

2016

Authors

De Sousa, S.M.C.
Kassahn, K.S.
McIntyre, L.C.
Chong, C.E.
Scott, H.S.
Torpy, D.J.

Editors

Advisors

Journal Title

Journal ISSN

Volume Title

Type:

Journal article

Citation

BMC Endocrine Disorders, 2016; 16(1):58-1-58-7

Statement of Responsibility

Sunita M. C. De Sousa, Karin S. Kassahn, Liam C. McIntyre, Chan-Eng Chong, Hamish S. Scott and David J. Torpy

Conference Name

Abstract

Background: The 46,XY female is characterised by a male karyotype and female phenotype arising due to any interruption in the sexual development pathways in utero. The cause is usually genetic and various genes are implicated. Case presentation: Herein we describe a 46,XY woman who was first diagnosed with androgen insensitivity syndrome (testicular feminisation) at 18 years; however, this was later questioned due to the presence of intact Müllerian structures. The clinical phenotype suggested several susceptibility genes including SRY, DHH, NR5A1, NR0B1, AR, AMH, and AMHR2. To study candidate genes simultaneously, we performed whole genome sequencing. This revealed a novel and likely pathogenic missense variant (p.Arg130Pro, c.389G>C) in SRY, one of the major genes implicated in complete gonadal dysgenesis, hence securing this condition over androgen insensitivity syndrome as the cause of the patient’s disorder of sexual development. Conclusion: This case highlights the emerging clinical utility of whole genome sequencing as a tool in differentiating disorders of sexual development.

School/Discipline

Dissertation Note

Provenance

Description

Data source: complete raw data from whole genome sequencing, available upon request

Access Status

Rights

© The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

License

Call number

Persistent link to this record