The thrombin receptor gene is centromeric to the common proximal breakpoint in patients with the 5q- syndrome: identification of a previously unrecognized chromosome 5 inversion.

The human thrombin receptor (TR) gene has previously been localized to band q13 of chromosome 5, a site that is at or contiguous with the common proximal breakpoint site identified in the majority of patients with the 5q- syndrome (dysmegakaryocytopoiesis and refractory anaemia). Since thrombin has putative effects on the growth and differentiation of megakaryocytes, we hypothesized that the phenotypic abnormalities in megakaryocytopoiesis observed in the 5q- syndrome may be partially explained by involvement of the TR gene in the interstitial deletion. We have utilized molecular and fluorescence in situ hybridization (FISH) analysis to study potential cytogenetic abnormalities of the thrombin receptor gene in patients demonstrating this abnormality. Dual-label FISH with a q12-specific genomic fragment and the TR gene was completed using interphase and metaphase cells from seven patients with a del(5)(q13q33). Our data demonstrate that the TR gene is located on the centromeric side of the common proximal breakpoint, and is grossly present in all patients with the affected 5q- chromosome. In addition, one of the seven patients demonstrated a small proximal rearrangement, most likely representing a paracentric inversion, which was not apparent by conventional cytogenetic techniques. The significance of these alterations is discussed.