title: Detection of low level sex chromosome mosaicism in Ullrich-Turner syndrome patients.
abstract: Ullrich-Turner syndrome (UTS) is most commonly due to a 45,X chromosome defect, but is also seen in patients with a variety of X-chromosome abnormalities or 45,X/46,XY mosaicism. The phenotype of UTS patients is highly variable, and depends largely on the karyotype. Patients are at an increased risk of gonadoblastoma when a Y-derived chromosome or chromosome fragment is present. Since constitutional mosaicism is present in approximately 50% of UTS patients, the identification of minor cell populations is clinically important and a challenge to laboratories. We identified 50 females with a 45,X karyotype as the sole abnormality or as part of a more complex karyotype. Twenty two (44%) had a 45,X karyotype; mosaicism for a second normal or structurally abnormal X was observed in 24 (48%) samples, and mosaicism for Y chromosomal material in 4 (8%) cases. To further investigate the possibility of mosaicism in the 22 patients with an apparently non-mosaic 45,X karyotype, we performed FISH using centromere probes for the X and Y chromosomes. A minor XX cell line was identified in 3 patients, and the 45,X result was confirmed in 19 samples. No samples with XY mosaicism were identified. We describe our validation process for a FISH assay to be used in clinical practice to identify XX or XY mosaicism. FISH as an adjunct to karyotype analysis provides a sensitive and cost-effective technique to identify sex chromosome mosaicism in UTS patients.
authors.affiliation: Cytogenetics Laboratory, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Wiktor
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Van Dyke
mesh_terms: D041321:Chromosomes, Human, X; D041322:Chromosomes, Human, Y; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D009006:Monosomy; D009030:Mosaicism; D014424:Turner Syndrome / Q000235:genetics*