A Dosage Sensitive Locus at Chromosome Xp21 Is Involved in Male to Female Sex Reversal

Bardoni, Barbara; Zanaria, Elena; Guioli, Silvana; Floridia, Giovanna; Worley, Kim C.; Tonini, G.; Ferrante, Emanuele; Chiumello, G; McCabe, Edward R.B.; Fraccaro, M.; Zuffardi, Orsetta; Camerino, Giovanna

doi:10.1097/00006254-199502000-00020

Cited by 394 publications

(55 citation statements)

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“…In addition, duplications of a region of the X chromosome containing DAX-1 cause dosage-sensitive sex reversal in XY individuals (MIM 300018). 3 Thus, it appears that DAX-1 is essential for the development of a functional hypothalamus-pituitary-gonadal axis. 1,2 Many different mutations in DAX-1 have been reported in sporadic and familial cases of AHC.…”

Section: Introductionmentioning

confidence: 99%

Partial defects in transcriptional activity of two novel DAX‐1 mutations in childhood‐onset adrenal hypoplasia congenita

Laissue

Copelli²,

Bergadá

et al. 2006

Clinical Endocrinology

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Section: Introductionmentioning

confidence: 99%

Partial defects in transcriptional activity of two novel DAX‐1 mutations in childhood‐onset adrenal hypoplasia congenita

Laissue

Copelli²,

Bergadá

et al. 2006

Clinical Endocrinology

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“…The SOX9 gene when mutated causes campomelic dysplasia together with gonadal dysgenesis in 46,XY subjects (8,9), while a SOX9 duplication is sufficient to cause testis development in a 46,XX embryo (10). WNT4 (11) and NR0B1 (nuclear receptor subfamily 0, group B, member 1, also known as DAX1) locus duplications are responsible for 46,XY gonadal dysgenesis (12), while mutations of NR0B1 cause congenital adrenal hypoplasia (13) and hypogonadic hypogonadism (14). Mutations in WNT4 have been reported in women with absence of uterus and signs of androgen excess (15,16).…”

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confidence: 99%

Gene dosage imbalances in patients with 46,XY gonadal DSD detected by an in‐house‐designed synthetic probe set for multiplex ligation‐dependent probe amplification analysis

et al. 2008

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The development of a testis requires the proper spatiotemporal expression of the SRY gene and other genes that act in a dosage-sensitive manner. Mutations in the SRY gene account for only 10-15% of patients with 46,XY gonadal disorder of sex development (DSD). To enable the diagnostics of deletions and duplications of genes known to be involved in different forms of DSD, we developed a synthetic probe set for multiplex ligation-dependent probe amplification (MLPA) analysis. Here, we report the results from the analysis of 22 patients with 46,XY gonadal DSD. The analysis with the DSD probe set has led to the identification of two copy number variations, an 800-kb NR0B1 (DAX1) locus duplication on Xp21 in a patient with isolated partial gonadal dysgenesis and a duplication of the SRD5A2 gene that represents a rare normal variant. The described MLPA kit represents an optimal complement to DNA sequence analysis in patients with DSD, enabling screening for deletions and duplications of several genes simultaneously. Furthermore, the second identification of an NR0B1 locus duplication in a patient with isolated gonadal dysgenesis, without dysmorphic features and/or mental retardation, highlights the importance of evaluating NR0B1 duplication in patients with gonadal dysgenesis.

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“…In mice, the knockout phenotype includes not only adrenal hypoplasia but also gonadal dysgenesis (15). When duplicated, 46, XY humans develop gonadal dysgenesis and male-to-female sex reversal, a phenomenon that requires significantly greater overexpression in mice (14,16,17). In potential explanation, expression of the NROB1 gene varies between humans and mice.…”

Section: Understanding the Normal Human Developmental Process Sex Detmentioning

confidence: 99%

Human embryo and early fetus research

Ostrer

Wilson

2006

Clinical Genetics

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Studies of human embryos and fetuses have highlighted developmental differences between humans and model organisms. In addition to describing the normal biology of our own species, a justification in itself, studies of early human development have aided identification of candidate disease genes mapped by positional cloning strategies, understanding pathophysiology, where human disorders are not faithfully reproduced by models in other species, and, more recently, potential therapies based on human embryonic stem and embryonic germ cells. In this article, we review these applications. We also discuss when and how to study human embryo and early fetuses and some of the regulations of this research.

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A Dosage Sensitive Locus at Chromosome Xp21 Is Involved in Male to Female Sex Reversal

Cited by 394 publications

References 0 publications

Partial defects in transcriptional activity of two novel DAX‐1 mutations in childhood‐onset adrenal hypoplasia congenita

Partial defects in transcriptional activity of two novel DAX‐1 mutations in childhood‐onset adrenal hypoplasia congenita

Gene dosage imbalances in patients with 46,XY gonadal DSD detected by an in‐house‐designed synthetic probe set for multiplex ligation‐dependent probe amplification analysis

Human embryo and early fetus research

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