Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012:2012:504904.
doi: 10.1155/2012/504904. Epub 2012 Feb 28.

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

Michela Barbaro  1 , Jackie Cook, Kristina Lagerstedt-Robinson, Anna Wedell
Affiliations

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

Michela Barbaro et al. Int J Endocrinol. 2012.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Family pedigree. Pedigree of a family with two sisters with 46,XY gonadal dysgenesis. +DAX1 indicates the subjects that carry the X chromosome containing the NR0B1 locus duplication. XX and XY have been added underneath some subjects indicating a 46,XX or 46,XY karyotype, respectively. Mandatory female carriers and potential carriers are marked.
Figure 2
Figure 2
Comparison of NR0B1 locus duplications. Representation from the UCSC genome browser (NCBI36/hg18) of the NR0B1 locus on Xp21.2. The probes that delineate the breakpoints in the three independent families identified by our group are represented by red vertical lines. The horizontal blue line represents the extension of the duplication in the family here described, the green lines represent the duplicated regions previously described by our group, and the orange lines represent the two duplications identified by array CGH in patients with isolate 46,XY GD by other groups. The C and P at the right ends of the lines indicate if the GD was complete or partial, respectively.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bardoni B, Zanaria E, Guioli S, et al. A dosage sensitive locus at chromosome Xp21 is involved in male to female sex reversal. Nature Genetics. 1994;7(4):497–501. - PubMed
    1. Dabovic B, Zanaria E, Bardoni B, et al. A family of rapidly evolving genes from the sex reversal critical region in Xp21. Mammalian Genome. 1995;6(9):571–580. - PubMed
    1. Swain A, Zanaria E, Hacker A, Lovell-Badge R, Camerino G. Mouse Dax1 expression is consistent with a role in sex determination as well as in adrenal and hypothalamus function. Nature Genetics. 1996;12(4):404–409. - PubMed
    1. Niakan KK, McCabe ERB. DAX1 origin, function, and novel role. Molecular Genetics and Metabolism. 2005;86(1-2):70–83. - PubMed
    1. Swain A, Narvaez V, Burgoyne P, Camerino G, Lovell-Badge R. Dax1 antagonizes Sry action in mammalian sex determination. Nature. 1998;391(6669):761–767. - PubMed

LinkOut - more resources