Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/91761
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Type: Journal article
Title: Interchromosomal insertional translocation at Xq26.3 alters SOX3 expression in an individual with XX male sex reversal
Author: Haines, B.
Hughes, J.
Corbett, M.
Shaw, M.
Innes, J.
Patel, L.
Gecz, J.
Clayton-Smith, J.
Thomas, P.
Citation: The Journal of Clinical Endocrinology & Metabolism, 2015; 100(5):E815-E820
Publisher: Endocrine Society
Issue Date: 2015
ISSN: 0021-972X
1945-7197
Statement of
Responsibility: 
Bryan Haines, James Hughes, Mark Corbett, Marie Shaw, Josie Innes, Leena Patel, Jozef Gecz, Jill Clayton-Smith, and Paul Thomas
Abstract: CONTEXT: 46,XX male sex reversal occurs in approximately 1: 20 000 live births and is most commonly caused by interchromosomal translocations of the Y-linked sex-determining gene, SRY. Rearrangements of the closely related SOX3 gene on the X chromosome are also associated with 46,XX male sex reversal. It has been hypothesized that sex reversal in the latter is caused by ectopic expression of SOX3 in the developing urogenital ridge where it triggers male development by acting as an analog of SRY. However, altered regulation of SOX3 in individuals with XX male sex reversal has not been demonstrated. PATIENTS AND METHODS: Here we report a boy with SRY-negative XX male sex reversal who was diagnosed at birth with a small phallus, mixed gonads, and borderline-normal T. Molecular characterization of the affected individual was performed using array comparative genomic hybridization, fluorescent in situ hybridization of metaphase chromosomes, whole-genome sequencing, and RT-PCR expression analysis of lymphoblast cell lines. RESULTS: The affected male carries ∼774-kb insertion translocation from chromosome 1 into a human-specific palindromic sequence 82 kb distal to SOX3. Importantly, robust SOX3 expression was identified in cells derived from the affected individual but not from control XX or XY cells, indicating that the translocation has a direct effect on SOX3 regulation. CONCLUSION: This is the first demonstration of altered SOX3 expression in an individual with XX male sex reversal and suggests that SOX3 can substitute for SRY to initiate male development in humans.
Keywords: Humans; Sex Chromosome Aberrations; Translocation, Genetic; Child, Preschool; Infant; Male; SOXB1 Transcription Factors; 46, XX Testicular Disorders of Sex Development
Description: First Published Online March 17, 2015
Rights: © 2015 by the Endocrine Society
RMID: 0030025319
DOI: 10.1210/jc.2014-4383
Appears in Collections:Paediatrics publications

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