title: Molecular analysis of Hb Q-H disease and Hb Q-Hb E in a Singaporean family.
abstract: Hb Q (alpha 74Asp-His) results from a mutation in the alpha-gene such that abnormal alpha Q-chains are synthesized. The alpha Q-chains combine with the normal Beta A-chains to form abnormal Hb alpha 2Q beta 2A (Hb Q). Hb Q-H disease is rare, and has been reported only in the Chinese. We report here a Chinese family, were the mother diagnosed with Hb Q-H disease and the father with Hb E heterozygosity and a child with Hb Q-E-thalassemia. Thalassemia screening of the mother's blood revealed a Hb level of 6.8g/dl with low MCV and MCH. Her blood film was indicative of thalassemia. Cellulose acetate electrophoresis showed Hb H and Hb Q with the absence of Hb A. Globin chain biosynthesis was carried out and alpha Q- and beta-chains were detected. Normal alpha- chains were absent. Digestion of the mother's DNA with Bam HI and Bgl II followed by hybridization with the 1.5 kb alpha-Pst probe showed a two alpha-gene deletion on one chromosome and the -alpha Q chain mutant with the -alpha 4.2 defect on the other chromosome. DNA amplification studies indicated the two-gene deletion to be of the -SEA/ defect. The patient was concluded to possess Hb Q-H disease (--SEA/-alpha 4.2Q). Cellulose acetate electrophoresis of the father's blood showed the presence of Hb A, F and E. Molecular analysis of the father's DNA confirmed an intact set of alpha-genes (alpha alpha/alpha alpha). Globin chain biosynthesis of fetal blood of their child showed gamma, beta A, beta E, alpha A and alpha Q-chains. Molecular analysis of the child's DNA showed one alpha-gene deletion, thus giving a genotype of alpha alpha/-alpha 4.2Q beta beta E.
authors.affiliation: Department of Pediatrics, National University of Singapore.
authors.forename: J
authors.initials: J
authors.lastname: Tan
authors.forename: J S
authors.initials: JS
authors.lastname: Tay
authors.forename: Y C
authors.initials: YC
authors.lastname: Wong
authors.forename: S K
authors.initials: SK
authors.lastname: Kham
authors.forename: N
authors.initials: N
authors.lastname: Bte Abd Aziz
authors.forename: S H
authors.initials: SH
authors.lastname: Teo
authors.forename: H B
authors.initials: HB
authors.lastname: Wong
mesh_terms: D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005312:Fetal Blood; D005319:Fetal Hemoglobin / Q000032:analysis; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D006446:Hemoglobin E / Q000032:analysis / Q000235:genetics*; D006447:Hemoglobin H / Q000032:analysis / Q000235:genetics*; D006453:Hemoglobinopathies / Q000097:blood* / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D017384:Sequence Deletion; D012846:Singapore
chemical_list: D017931:DNA Primers; D006455:Hemoglobins, Abnormal; C099422:hemoglobin Q; D005914:Globins; D006446:Hemoglobin E; D005319:Fetal Hemoglobin; D006447:Hemoglobin H