P-12

Prenatal diagnosis mosaic 45, X case with a marker chromosome

Joel Pinto^I; Maria Lina Moreira^I; Ana Barbosa^I; Vânia Ventura^I; Ana Paula Neto^I; Carla Ramalho^II; Alberto Barros^I; Sofia Dória^I

^IGenetics Department, Faculty of Medicine, University of Porto, Porto, Portugal
^IIObstetrics and Gynaecology Department, Faculty of Medicine, University of Porto, Porto, Portugal

jpinto@med.up.pt

Introduction: Small supernumerary marker chromosomes (sSMC) are structurally abnormal chromosomes that cannot be identified or characterized unambiguously by conventional banding cytogenetics. Generally the size is about or smaller than a chromosome 20, and molecular cytogenetic techniques are necessary for a comprehensive characterization. Prenatally ascertained sSMCs occur in 0.075%, and 0,044% in subsequently studied postnatal analysis. The overall risk of phenotypic abnormalities in prenatally ascertained sSMCs has been estimated to be about 13%. sSMC in Turner syndrome (sSMC) are very rare in the common population (1:100,000) – however, they can be observed with a 45and even 60-times higher frequency in infertile or intellectual disability patients, respectively. Even though sSMC derive from one of the sex chromosome in >99% of the cases and the majority form ring chromosome. There are also exceptional reports on sSMC derived from one of the autosomes. Thus, a detailed molecular cytogenetic marker chromosome characterization is needed to provide information on sSMC.

Methods: A 29-year-old primigravida woman underwent amniocentesis at 16 weeks of gestation due to a positive maternal biochemistry screening for trissomy 13 and 18, and the presence of a single umbilical artery. Karyotype (GTLbanding), aCGH (4x180k Agilent Human CGH Microarray) and FISH analysis (CEPX Spectrum Green) were sequentially performed in cultured amniocytes to better characterize this sSMC.

Results: Amniocentesis revealed a karyotype 45,X[22]/46,X,+mar[8]. Among 30 cultured amniocytes colonies, 8 contained the  sSMC,  whereas  the  remaining 22 colonies were 45,X. Using DNA extracted from cultured amniocytes, aCGH showed that the sSMC was originated from chromosome X and revealed a 19,81-Mb gene dosage increase at Xp11.21-Xq21.1. FISH analysis showed 41% (41/100) mosaicism for sSMC in cultured amniocytes and confirmed the identification of the sSMC as derivate from chromosome X.

Discussion: Althought sSMC are rare, this is a wellknown cytogenetic entity. So far, a detailed molecular cytogenetic characterization of sSMC by aCGH was only perfomed in a few cases. In this case, we could conclude that sSMC was derived from Xp11.21-Xq21.1 probably as a ring [r(X)(p11.21q21.1)] due to absence of telomeric regions. This sSMC (X) includes XIST region, allowing the inactivation of this chromosome. Once that it is very small being all the short arm and part of the long arm absent, it is expected that it is preferential inactivated instead of occurring random inactivation. This is in accordance with the absence of ultrasound abnormalities. Nevertheless, the inactivation pattern is not predictable. For the better characterization of this kind of sSMC (X), aCGH should always be performed allowing a more accurate genetic counseling.