Abstract
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.
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Disclosure of interests
Nothing to disclose
Contribution to Authorship
Gheona Altarescu was the principal investigator and responsible with the design of the methods, genetic counseling and analysis.
Orit Reish performed the original genetic diagnosis in the family.
E. Kasterstein, D. Komarovsky, A. Komsky, O. Bern, D. Strassburger performed all the embryo biopsy.
Paul Renbaum performed genetic analysis and manuscript preparation/editing
Ephrat Levy-Lahad- advice for molecular strategy manuscript editing
Raphael Ron El was also principle investigator and responsible of all the IVF management.
Ethics Approval
The PGD is performed in our medical center as routine medical procedure and is not experimental therefore IRB was not required.
Funding
Funding was obtained from the family seeking PGD.
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Capsule
A PGD protocol is presented for a paternal SHOX-related Haploinsufficiency with screening for trisomy 21. High recombination rates require multiple markers for analysis.
G. Altarescu and O. Reish contributed equally to the present work
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Altarescu, G., Reish, O., Renbaum, P. et al. Preimplantation genetic diagnosis (PGD) for SHOX-related haploinsufficiency in conjunction with trisomy 21 detection by molecular analysis. J Assist Reprod Genet 28, 233–238 (2011). https://doi.org/10.1007/s10815-010-9508-2
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DOI: https://doi.org/10.1007/s10815-010-9508-2