Molecular characterization of hereditary persistence of fetal hemoglobin in the Karen people of Thailand.
Hereditary persistence of fetal hemoglobin (HPFH) is the condition whereby a continuously active gamma-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 delta(beta) 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 beta- and gamma-globin genes, or the gamma-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 beta-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 beta-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 beta-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.
Trachoo
Objoon
O
Department of Medicine, Division of Medical Genetics and Molecular Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. objootra@ccme.or.th
Sura
Thanyachai
T
Sakuntabhai
Anavaj
A
Singhasivanon
Pratap
P
Krudsood
Srivicha
S
Phimpraphi
Waraphon
W
Krasaesub
Somporn
S
Chanjarunee
Suporn
S
Looareesuwan
Sornchai
S
D000328:Adult; D044466:Asian People; D001483:Base Sequence; D017931:DNA Primers; D005006:Ethnicity; D005260:Female; D005319:Fetal Hemoglobin / Q000235:genetics*; D005914:Globins / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D012016:Reference Values; D017384:Sequence Deletion; D013785:Thailand; D017086:beta-Thalassemia / Q000235:genetics*
D017931:DNA Primers; D005914:Globins; D005319:Fetal Hemoglobin