A large deletion encompassing the entire α-like globin gene cluster in a family of northern european extraction

Abstract

We describe a new deletional form of α thalassemia segregating in three generations of a family of northern European origin. A full-term female girl had hypochromic, mlcrocytic anemia since early Infancy associated with delayed language development, slow growth and weight gain. Hematologic studies suggested the presence of α thalassemia. Gene-blotting studies showed no abnormal α-like globin gene fragments; however, studies of inheritance of informative polymorphic restriction fragments using ζ, α and 3′-α-hypervariable region (3′-HVR) probes showed evidence for an extensive deletion encompassing the entire α-like globin gene cluster. The 3′ breakpoint of this deletion maps beyond the 3′-HVR, a region implicated as a hot spot for the generation of other large deletional events within the α-like cluster. The 5′ breakpoint maps at least 10 kilobases (kb) 5′ to the ζ-globin gene. The minimum size estimate for this deletion is greater than 47 kilobases. © 1988 IRL Press Ltd.