GENETIC-HETEROGENEITY IN HETEROCELLULAR HEREDITARY PERSISTENCE OF FETAL HEMOGLOBIN

A large English pedigree in which heterocellular hereditary persistenc e of fetal hemoglobin (HPFH) segregates is described, beta-globin clus ter deletions and gamma gene promoter mutations associated with HPFH h ave been excluded. Of particular importance in this pedigree is the ab sence of any cosegregating hemoglobinopathy, thus allowing observation of the segregation pattern of this form of HPFH without the complicat ing effect of a beta-globin gene mutation, Information gained in this study confirms that the extent of elevation of hemoglobin (Hb) F and F cells varies between affected individuals. There are one example of i ncomplete penetrance and three examples of father-to-son transmission, thus excluding X-linked inheritance, Consistent with previous reports , the most likely mode of inheritance is autosomal codominant, Linkage studies using a beta-globin cluster microsatellite show no evidence o f linkage to this chromosomal region implicating the presence of trans -acting regulatory factor(s). We have recently mapped one such locus t o the chromosome 6q region in a very large Asian-Indian pedigree, Link age to chromosome 6q in the English pedigree was excluded, thus indica ting the presence of genetic heterogeneity in heterocellular HPFH. (C) 1997 by The American Society of Hematology.