Distal 5q Trisomy resulting from an X;5 translocation detected by chromosome painting

Abstract

The distal 5q trisomy genotype has been associated with clinical signs including short stature; microcephaly; downward palpebral slant; strabismus; prominent, widened nasal bridge; long, flat philtrum; long, thin upper lip with downturned corners; large, low-set, dysplastic ears; limb and joint malformations; cardiopulmonary abnormalities; abdominal herrnias; and mental retardation. We describe a 13-year-old female with an apparently de nova unbalanced translocation resulting in the presence of additional chromosomal material on the short arm of the X chromosome, detected by conventional G-banding studies. She exhibits several of these features: short stature, prominent nasal bridge, flat philtrum, thin upper lip, limb and cardiac malformations. Fluorescent in situ hybridization (FISH) using the Chromoprobe™ Multiprobe-M protocol demonstrates that the additional chromosomal material originates from chromosome 5. The karyotype of this patient is now established to be 46,X,der(X)t(X;5)(p22.3;q33). This is the first case of distal 5q trisomy arising from a translocation with the X chromosome.Replication studies on this patient show that the derivative t(X;5) chromosome is late replicating in almost all cells examined, which indicates that this chromosome is preferentially inactivated. However, the translocated segment of chromosome 5 appears to be early replicating, which implies that the trisomic 5q segment is transcriptionally active. We cannot determine from these studies whether all or only some genes in this segment are expressed, but this patient's relatively mild clinical signs suggest that the critical region(s) which contribute to the distal 5q trisomy phenotype are at least partially suppressed.