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Variability of sexual phenotype in 46,XX(SRY+) patients: the influence of spreading X inactivation versus position effects
  1. A Sharp1,
  2. K Kusz2,
  3. J Jaruzelska2,
  4. W Tapper3,
  5. M Szarras-Czapnik4,
  6. J Wolski5,
  7. P Jacobs1
  1. 1Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ, UK
  2. 2Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60–479, Poznan, Poland
  3. 3Division of Human Genetics, University of Southampton Medical School, Southampton SO16 6YD, UK
  4. 4The Children’s Memorial Health Institute, Warsaw, Poland
  5. 5Infertility Center Novum, Warsaw, Poland
  1. Correspondence to:
 Andrew Sharp
 University of Washington, Department of Genome Sciences, HSB K360, Box 357730, 1705 North East Pacific Street, Seattle, WA 98195, USA;

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During male meiosis the X and Y chromosomes pair along much of their length, with a single obligatory recombination event usually occurring in the pseudo-autosomal region (PAR) at the tip of Xp and Yp,1 thus maintaining identity of the sex chromosome PARs.2

Occasionally illegitimate crossover occurs outside the PAR, resulting in the transfer of Y specific sequences onto the X chromosome. Such translocations between distal Xp and Yp occur relatively frequently, resulting in the generation of 46,XX individuals, the majority of whom display an overtly male phenotype due to transfer of the SRY gene onto the short arm of the paternal X.3–5 However, a small number of Yp translocations are associated with hermaphroditism, defined as the presence of both testicular and ovarian tissue in the same individual.6–8 While the size of the translocated Yp fragment in XX males is variable,9 a recombination hotspot defined by the X/Y homologous genes PRKX and PRKY accounts for approximately one third of cases.10,11 A common inversion polymorphism in proximal Yp flanks this recombination hotspot.12–14

In XX individuals one of the two X chromosomes is inactivated in early embryonic development as a mechanism of dosage compensation for sex linked genes.15 This results in the conversion of the inactive X to a heterochromatic state and the transcriptional silencing of most of the genes upon it.16 Studies of X;autosome translocations have demonstrated that the X inactivation signal is also capable of spreading into cis linked chromatin in a variable manner,17–19 and it has been proposed that spreading of X inactivation into the translocated Yp segment carrying the SRY gene could account for the incomplete masculinisation which is occasionally observed in individuals with X/Y translocations.3,7,8 While evidence to support this …

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  • This work was supported by grants from The Wellcome Trust (Ref. 058387) and Medical Research Council (Ref. G9801327).

  • Competing interests: none declared