Fetal Cystic Hygroma Associated with Terminal 2p25.1 Duplication and Terminal 3p25.3 Deletion: Cytogenetic, Fluorescent in Situ Hybridization and Microarray Familial Characterization of Two Different Chromosomal Structural Rearrangements

Abstract

We report a prenatally diagnosed case of partial trisomy 2p and partial monosomy 3p, resulting from unbalanced translocation (2;3)(p25.1;p25.3) of paternal origin. Parents were non consanguineous Caucasians, with familial history of recurrent miscarriages on the father's side. Detailed sonographic examination of the fetus showed a septated cystic hygroma measuring 6 mm at 13 weeks' gestation. Karyotyping and fluorescent in situ hybridization (FISH) analysis of cultured amniotic fluid cells revealed an unbalanced translocation der(3)t(2;3)(p25.1; p25.3) and apparently balanced inv(3)(p13p25.3) in a fetus. Parental cytogenetic evaluation using karyotyping and FISH analysis showed the presence of both a balanced translocation and a paracentric inversion in father t(2;3) (p25.1;p25.3) inv(3)(p13p25.3). Microarray analysis showed a 11.6 Mb deletion at 3p26.3-p25.3 and duplication of 10.5 Mb at the 2p25.3-p25 region. The duplicated region at 2p25.1p25.3 contains 45 different genes, where 12 are reported as OMIM morbid genes with different phenotypical implications. The deleted region at 3p26.3-p25.3 contains 65 genes, out of which 27 are OMIM genes. Three of these (CNTN4, SETD5 and VHL) were curated by Clingene Dosage Gene Map and were given a high haplo-insufficiency score. Genes affected by the unbalanced translocation could have contributed to some specific phenotypic changes of the fetus in late pregnancy. The application of different cytogenetic methods was essential in our case, allowing the detection of different types of structural chromosomal aberrations and more thorough genetic counseling for future pregnancies.

Keywords: Array comparative genomic hybridization (aCGH); Chromosome 2; Chromosome 3; Molecular karyotyping.

Figure 1

(A) Partial karyotype with accompanied ideograms showing balanced translocation (2;3)(p25.1;p25.3) and paracentric inversion of chromosome 3 in the father. (B) Metaphase FISH on paternal peripheral blood lymphocytes using whole-chromosome painting probe for chromosome 3 (green label) and chromosome 3 specific centromere probe (red label). The arrow indicates derivative chromosome 2p resulting from 2p;3p reciprocal translocation. (C) Array comprehensive genomic hybridization analysis of cultured amniotic fluid cells: detailed view of 2(p25.1-p25.3) gain. (D) The 3(p25.3-p26.3) deletion (image from Cytoreport generated by Cytogenomics software; Agilent Technologies).