Abstract for presentation at 11th International Congress of Human Genetics

Prenatal detection of nullisomy for distal Xp22.3 in a male fetus with short limbs and a maternally derived der(X)t(X;Y)(p22.33;q11.2)

  • Ms Rosemarie Kelly, Molecular and Cytogenetics Unit, SEALS, Prince of Wales Hospital, Sydney, NSW, Australia
  • Mr Ryan Dashwood, Molecular and Cytogenetics Unit, SEALS, Prince of Wales Hospital, Sydney, NSW, Australia
  • Mr Alex Kovacic, Molecular and Cytogenetics Unit, SEALS, Prince of Wales Hospital, Sydney, NSW,, Australia
  • Mr Peter Taylor, Molecular and Cytogenetics Unit, SEALS, Prince of Wales Hospital, Sydney, NSW, Australia
  • Dr Robert Ogle, Molecular and Clinical Genetics Unit, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  • Dr Tony Roscioli, Molecular and Clinical Genetics Unit, Royal Prince Alfred Hospital, Sydney, NSW, Australia
  • Dr Michael Fietz, Dept of Genetic Medicine, Women and Children’s Hospital, Adelaide, South Australia, Australia
  • Dr Moh-Ying Yip, Molecular and Cytogenetics Unit, SEALS, Prince of Wales Hospital, Sydney, NSW, Australia

    • Purpose: We present the prenatal detection of a maternally derived der(X)t(X;Y)(p22.33;q11.2) in a 25 week male fetus with short long bones (<3rd percentile), a normal chest circumference and mild cerebral ventriculomegaly. The 28 year old mother had short stature, normal intelligence, mesomelic shortening without a Madelung deformity. There was a family history of maternal short stature. Both fetus and mother, carriers of the der(X)t(X;Y) were further investigated for the loss of genes in the distal short arm of the X chromosome.
    Methods: Molecular genetic testing for FGFR3 skeletal dysplasias was carried out prior to the availability of the karyotype. Cytogenetic studies include distamycin A treatment for detecting Y heterochromatin and fluorescence in-situ hybridisation (FISH) using probes for XpTEL and KAL1(Kallman gene). Amniocytes were also screened for steroid sulphatase (STS) deficiency.
    Results: The male fetus has a 46,Y,der(X)t(X;Y)(p22.33;q11.2)mat karyotype in which the maternally derived X chromosome had mainly non-coding Y heterochromatin at its distal short arm end. Loss of the Xp telomere but an intact KAL1 locus was found on FISH. Amniocytes were deficient for the STS enzyme, suggesting the Xp break to be between STS and KAL1. FGFR3 skeletal dysplasia screening detected a previously unreported FGFR3 intron 15 SNP, which was also present in the father.
    Conclusions: The pregnancy is ongoing. A review of the clinical phenotype involving short stature, bony deformities, ichthyosis and mental retardation associated with loss of terminal Xp genes will be presented.

    Conference Organiser - ICMS Pty Ltd