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International Journal of Endocrinology
Volume 2012, Article ID 504904, 7 pages
Research Article

Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal Dysgenesis

1Department of Molecular Medicine and Surgery, Karolinska Institut, Karolinska University Hospital, CMM L8:02, 17176 Stockholm, Sweden
2Department of Clinical Genetics, Sheffield Children's Hospital, Sheffield S 102 TH, UK

Received 31 August 2011; Revised 21 November 2011; Accepted 21 November 2011

Academic Editor: Gil Guerra-Junior

Copyright © 2012 Michela Barbaro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


A 160 kb minimal common region in Xp21 has been determined as the cause of XY gonadal dysgenesis, if duplicated. The region contains the MAGEB genes and the NR0B1 gene; this is the candidate for gonadal dysgenesis if overexpressed. Most patients present gonadal dysgenesis within a more complex phenotype. However, few independent cases have recently been described presenting with isolated XY gonadal dysgenesis caused by relatively small NR0B1 locus duplications. We have identified another NR0B1 duplication in two sisters with isolated XY gonadal dysgenesis with an X-linked inheritance pattern. We performed X-inactivation studies in three fertile female carriers of three different small NR0B1 locus duplications identified by our group. The carrier mothers did not show obvious skewing of X-chromosome inactivation, suggesting that NR0B1 overexpression does not impair ovarian function. We furthermore emphasize the importance to investigate the NR0B1 locus also in patients with isolated XY gonadal dysgenesis.