YAC and cosmid FISH mapping of an unbalanced chromosomal translocation causing partial trisomy 21 and Down syndrome

Most cases of Down syndrome (DS) result from a supernumerary chromosome 21; however, there are rare cases in which DS is due to partial trisomy of chromosome 21, involving various segments of the chromosome. The characterization of cases of DS that are due to partial trisomy 21 allows the phenotype to be correlated with the genotype. We present a case with features of DS and a partial trisomy of chromosome 21 inherited from a paternal balanced translocation involving chromosomes 13 and 21. Fluorescence in situ hybridization analysis using yeast artificial chromosome (YAC) probes mapped the breakpoint to 21q22.1, within YAC 230E8, which contains markers CBR, D21S333 and D21S334. Further mapping using cosmids positioned the breakpoint proximal to CBR. The patient was also monosomic for the distal portion of chromosome 13 (q33-qter). Many phenotypic features of DS were present including hypotonia, flat occiput, flat facies, up-slanted palpebral fissures, epicanthic folds, flat nasal bridge, macroglossia, open mouth, small ears and a heart murmur. This case further supports the contention that the majority of the phenotypic features of DS map to 21q22-qter and further refines the location of some of them. In addition to the DS phenotype, the patient had a prominent upper maxilla with protruding upper incisors, and low levels of the coagulation factors VII and X, consistent with a syndrome resulting from monosomy 13q33-qter. Since some features overlap between the two syndromes, including severe mental retardation, it is unclear to what extent monosmy for 13q33-qter, trisomy for 21q22.1-qter, or a combination of both, contributed to the common features of the phenotype.