Molecular Characterization of Hereditary Persistence of Fetal Hemoglobin in the Karen People of Thailand

Abstract

Hereditary persistence of fetal hemoglobin (HPFH) is the condition whereby a continuously active γ‐globin gene expression leads to elevated fetal hemoglobin (Hb F) levels in adult life [Stamatoyannopoulos G, Grosveld F. Hemoglobin switching. In: Stamatoyannopoulos G, Majerus PW, Perlmutter RM, Varmus H, eds. The Molecular Basis of Blood Diseases. Philadelphia: W.B. Saunders, 2001:135–182; Wood WG. Hereditary persistence of fetal hemoglobin and δβ thalassemia. In: Steinberg MH, Forget BG, Higgs DR, Nagel RL, eds. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge: Cambridge University Press, 2001:356–388; and Weatherall DJ, Clegg JB. Hereditary persistence of fetal hemoglobin. In: Weatherall DJ, Clegg JB, eds. The Thalassaemia Syndromes. Oxford: Blackwell Scientific Publishers, 1981:450–507]. The condition is caused either by mutation of the β‐ and γ‐globin genes, or the γ‐gene controlled region on other chromosomes. Several families with this condition have been reported from Vietnam, Cambodia and China, and the Southeast Asian mutation (or HPFH‐6), a 27 kb deletion, was demonstrated. Here we report on a mother and her daughter of the Karen ethnic group with high levels of Hb F, living in the Suan Pueng District on the border of Thailand and Myanmar. Genotyping showed a heterozygosity for the 27 kb deletion of the β‐globin gene. Their conditions have been confirmed by gap polymerase chain reaction (PCR) with three oligonucleotide primers recently developed by Xu et al. [Xu X‐M, Li Z‐Q, Liu Z‐Y, Zhong X‐L, Zhao Y‐Z, Mo Q‐H. Molecular characterization and PCR detection of a deletional HPFH: application to rapid prenatal diagnosis for compound heterozygotes of this defect with β‐thalassemia in a Chinese family. Am J Hematol 2000; 65:183–188.], and a DNA sequencing method. Thus far there has been no official report of the HPFH‐6 anomaly from Thailand. The compound heterozygosity of β‐thalassemia (thal) and hereditary persistence of Hb F causes the phenotype of thalassemia intermedia; in contrast, homozygotes for this anomaly show only mild microcytic anemia. Hence, genetic counseling for hereditary persistence of Hb F carriers is needed for family planning.