TITLE:
SRY in an XX male does not influence random chromosome X inactivation: Cytogenetic evidence. Definition of the boundaries of the translocated Y segment through FISH and PCR-RT in a case report and review of the literature
AUTHORS:
Mariano Stabile, Vincenzo Altieri, Rosa Salzillo, Panfilo Marrollo, Guglielmo Stabile, Tina Iuorio, Bianca Moscato
KEYWORDS:
XX Male; SRY; Translocation X-Y; X Chromosome Inactivation; Y Chromosome
JOURNAL NAME:
Open Journal of Genetics,
Vol.3 No.2C,
August
7,
2013
ABSTRACT: We report a case of an SRY positive XX male. The phenotype was completely masculinised except for the reduced facial hair; testes were small, and azoospermia was present. The patient’s metaphases, coloured with acridine-orange to reveal the late replicating X chromosome, were sequentially hybridised with SRY and X centromeric probes: a random X chromosome inactivation pattern (XCIP) was present, with SRY present about half the time on both the active X and the inactive X. The most likely hypothesis is that the translocated SRY gene escaped inactivation as part of the entire X Pseudo Autosomal telomeric Region 1 (PAR 1). This hypothesis can explain the masculine phenotype, which would be incompatible with a halved expression of SRY. Review of the literature about the association of 46, XX males with a specific XCI pattern is made. The analysis of region AZF and QF-PCR for Y polymorphic loci allowed us to define the boundaries of the translocated Y segment as restricted to the region around the SRY locus. Chromosomal fragility analysis, using SCE (Sister Chromatid Exchanges), ruled out chromosomal fragility as a predisposing factor in the proband’s father; in addition, no chromosome Y polymorphic variant (inversion, Y qh ＋/﹣), was present in the proband’s father. However, like the AZF region c microdeletions and PRKX/PRKY translocation XX males, a particular Y haplotype could be also in this case a predisposing factor.