Concordance of a Point Mutation 5’ to the “y Globin Gene With G#y + Hereditary Persistence of Fetal Hemoglobin in the Black Population

Hereditary persistence of fetal hemoglobin (HPFH) is a genetically heterogeneous and clinically benign condition characterized by persistent expression of fetal hemoglobin (Hb F) into adulthood. In the G, + type. no major deletions in the globin gene cluster occur; adult heterozygotes produce approximately 20% Hb F. which results from overproduction of chains. with no apparent increase in production from the adjacent gene. We have recently described a point mutation 202 base pairs 5’ to the cap site of the gene in an individual with G.. fl+ HPFH. This mutation abolishes a normal Apal restriction endonuclease site. and thus can be detected by blotting of genomic DNA. We present here further data on the Apal mutation: (1 ) It occurs in six of seven families with HPFH. (2) In three families. detailed haplotype analysis using 1 1 polymorphic