A large deletion encompassing the entire alpha-like globin gene cluster in a family of northern European extraction.
We describe a new deletional form of alpha thalassemia segregating in three generations of a family of northern European origin. A full-term female girl had hypochromic, microcytic anemia since early infancy associated with delayed language development, slow growth and weight gain. Hematologic studies suggested the presence of alpha thalassemia. Gene-blotting studies showed no abnormal alpha-like globin gene fragments; however, studies of inheritance of informative polymorphic restriction fragments using zeta, alpha and 3'-alpha-hypervariable region (3'-HVR) probes showed evidence for an extensive deletion encompassing the entire alpha-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 alpha-like cluster. The 5' breakpoint maps at least 10 kilobases (kb) 5' to the zeta-globin gene. The minimum size estimate for this deletion is greater than 47 kilobases.
Fortina
P
P
Division of Hematology, Children's Hospital, Philadelphia, PA.
Delgrosso
K
K
Rappaport
E
E
Poncz
M
M
Ballas
S K
SK
Schwartz
E
E
Surrey
S
S
D002675:Child, Preschool; D002872:Chromosome Deletion; D005260:Female; D005858:Germany; D005914:Globins / Q000235:genetics*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D005810:Multigene Family; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D013789:Thalassemia / Q000097:blood / Q000235:genetics*
D006454:Hemoglobins; D005914:Globins