46,XY,18q+/46,XY,18q- mosaicism in a fragile X prenatal diagnosis

We describe a fetus with confined placental mosaicism for 46,XY,dup(18)(q21q23)/46,XY, del(18)(q21) in which finally the 18q- cell line formed the embryo. This prenatal diagnosis was performed on a pregnant woman carrying a premutation in the FMR1 gene. The purpose of the current study was to characterise the final fetus genotype and to discuss how this chromosomal abnormality was originated.

Conventional cytogenetic analyses were performed from chorionic villi, amniocytes, and fetal blood samples in order to establish the fetal chromosome constitution. Molecular studies with microsatellite markers and CGH were carried out to this end. PCR and Southern blot were used to analyse the CGG-repeat region of the FMR1 gene.

An initial chorionic villi sample analysis showed a normal allele for the fragile X syndrome, but an abnormal 46,XY,dup(18)(q21q23) karyotype. Amniocentesis was subsequently performed, and a different 46,XY,del(18)(q21) cell line was detected. Re-examination of original chorionic villi sample evidenced a mosaicism for 46,XY,dup(18)(q21q23)/46,XY,del(18)(q21). Molecular findings allowed us to determine that the deletion expands at least 20 Mb and that it is paternally inherited.

Two different cell lines with structural abnormalities on chromosome 18 were formed as a consequence of an unequal sister chromatid exchange during the first post-zygotic division. This case reinforces the necessity of performing a karyotype in all prenatal diagnosis even when the indication is for a monogenic disease.