Preimplantation genetic diagnosis (PGD) for SHOX-related haploinsufficiency in conjunction with trisomy 21 detection by molecular analysis

J Assist Reprod Genet. 2011 Mar;28(3):233-8. doi: 10.1007/s10815-010-9508-2. Epub 2010 Dec 1.


Purpose: Development of a molecular PGD protocol for a male with an X-linked deletion in the SHOX gene region, located in the pseudoautosomal region of the X/Y chromosomes. Due to excessive recombination in this region, the deletion can be found in male offspring.

Methods: We developed a 13 marker multiplex fluorescent PCR protocol: 3 markers within the deleted SHOX region, 5 flanking markers, 3 informative markers on chromosome 21 (advanced maternal age) and 2 markers for sex determination.

Results: Of four embryos, two wild type males, diploid for chromosome 21 were transferred resulting in twin boys. One embryo was an affected female and another embryo was Turner. Amniocentesis confirmed the implanted embryos were males (46XY), with no recombinations.

Conclusions: While many X-linked disorders can be analyzed by sexing, genes located in the pseudoautosomal regions have high XY recombination rates, requiring multiple markers to enable an accurate diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromosomes, Human, Pair 21
  • Down Syndrome / diagnosis*
  • Embryo Transfer / methods
  • Female
  • Fertilization in Vitro
  • Growth Disorders / genetics
  • Haploinsufficiency*
  • Homeodomain Proteins / genetics*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Male
  • Pregnancy
  • Preimplantation Diagnosis*
  • Short Stature Homeobox Protein


  • Homeodomain Proteins
  • SHOX protein, human
  • Short Stature Homeobox Protein