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

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 pheno...

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Main Authors: Michela Barbaro, Jackie Cook, Kristina Lagerstedt-Robinson, Anna Wedell
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2012/504904
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author Michela Barbaro
Jackie Cook
Kristina Lagerstedt-Robinson
Anna Wedell
author_facet Michela Barbaro
Jackie Cook
Kristina Lagerstedt-Robinson
Anna Wedell
author_sort Michela Barbaro
collection DOAJ
description 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.
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publishDate 2012-01-01
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spelling doaj-art-43d82f0e6ca049d184377d9a2f1f277f2025-08-20T02:17:37ZengWileyInternational Journal of Endocrinology1687-83371687-83452012-01-01201210.1155/2012/504904504904Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal DysgenesisMichela Barbaro0Jackie Cook1Kristina Lagerstedt-Robinson2Anna Wedell3Department of Molecular Medicine and Surgery, Karolinska Institut, Karolinska University Hospital, CMM L8:02, 17176 Stockholm, SwedenDepartment of Clinical Genetics, Sheffield Children's Hospital, Sheffield S 102 TH, UKDepartment of Molecular Medicine and Surgery, Karolinska Institut, Karolinska University Hospital, CMM L8:02, 17176 Stockholm, SwedenDepartment of Molecular Medicine and Surgery, Karolinska Institut, Karolinska University Hospital, CMM L8:02, 17176 Stockholm, SwedenA 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.http://dx.doi.org/10.1155/2012/504904
spellingShingle Michela Barbaro
Jackie Cook
Kristina Lagerstedt-Robinson
Anna Wedell
Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal Dysgenesis
International Journal of Endocrinology
title Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal Dysgenesis
title_full Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal Dysgenesis
title_fullStr Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal Dysgenesis
title_full_unstemmed Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal Dysgenesis
title_short Multigeneration Inheritance through Fertile XX Carriers of an NR0B1 (DAX1) Locus Duplication in a Kindred of Females with Isolated XY Gonadal Dysgenesis
title_sort multigeneration inheritance through fertile xx carriers of an nr0b1 dax1 locus duplication in a kindred of females with isolated xy gonadal dysgenesis
url http://dx.doi.org/10.1155/2012/504904
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AT jackiecook multigenerationinheritancethroughfertilexxcarriersofannr0b1dax1locusduplicationinakindredoffemaleswithisolatedxygonadaldysgenesis
AT kristinalagerstedtrobinson multigenerationinheritancethroughfertilexxcarriersofannr0b1dax1locusduplicationinakindredoffemaleswithisolatedxygonadaldysgenesis
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