Prenatal diagnosis and characterization of an unbalanced whole arm translocation resulting in monosomy for 18p

Monosomy for the short arm of chromosome 18 is one of the most frequent aut osomal deletions observed. While most cases result from terminal deletion o f 18p, 16% of cases reported were as a result of an unbalanced whole arm tr anslocation resulting in monosomy 18p. The origin and structure of these de rivative chromosomes were reported in only a few cases. We report the prena tal diagnosis and characterization of a new case of monosomy 18p as a resul t of an unbalanced whole arm translocation. Amniocentesis was performed at 15 weeks of gestation on a 34-year-old woman initially referred for advance d maternal age. Holoprosencephaly was identified by ultrasound at the time of amniocentesis, Karyotype analysis showed an unbalanced whole arm translo cation between the long arm of one chromosome IS and the long arm of one ch romosome 22, 45,XX,der(18;22)(q10;q10), in all metaphases. In effect, the f etus had monosomy for 18p, Parental karyotypes were normal, suggesting a de novo origin for the der(18;22), Fluorescence in situ hybridization (FISH) analysis was performed with alpha -satellite probes D18Z1 and D14Z1/D22Z1 t o identify the origin of the centromere on the der(18;22). Signal was obser ved with both probes, indicating that the centromere was composed of alpha -satellite DNA from both constituent chromosomes. Genotyping of the fetus a nd her parents with chromosome 18p STS marker D18S391 showed only the pater nal 187 bp allele was present in the fetus, indicating that it was the mate rnal chromosome 18 involved in the der(18;22). This case and previous repor ts show that de novo unbalanced whole arm translocations are more likely to retain alpha -satellite sequences from the; two chromosomes involved.