title: A C----T substitution at nt--101 in a conserved DNA sequence of the promotor region of the beta-globin gene is associated with "silent" beta-thalassemia.
abstract: Sequence analyses and dot-blot analyses with synthetic oligonucleotide probes have identified eight individuals in three Turkish families and one Bulgarian family with one chromosome having a C----T mutation at nucleotide position--101 relative to the Cap site of the beta-globin gene. This nucleotide is part of one of the conserved blocks of nucleotides within the promoter region; in vitro expression analyses with the chloramphenicol acetyltransferase system showed that this substitution will decrease the effectiveness of transcription. Five subjects had a thalassemia intermedia due to the additional presence of a known classical high hemoglobin (Hb) A2 beta-thalassemia mutation on the second chromosome; their hematologic condition was relatively mild. The three persons with a heterozygosity for the--101 C----T mutation had normal hematologic data without microcytosis but with high-normal levels of Hb A2 and a mild imbalance in chain synthesis. The newly discovered mutation is considered one of the silent types of beta-thalassemia. It is relatively rare because it was absent among several hundred normal and beta-thalassemia chromosomes.
authors.affiliation: Department of Cell and Molecular Biology, College of Georgia, Augusta.
authors.forename: J M
authors.initials: JM
authors.lastname: Gonzalez-Redondo
authors.forename: T A
authors.initials: TA
authors.lastname: Stoming
authors.forename: A
authors.initials: A
authors.lastname: Kutlar
authors.forename: F
authors.initials: F
authors.lastname: Kutlar
authors.forename: K D
authors.initials: KD
authors.lastname: Lanclos
authors.forename: E F
authors.initials: EF
authors.lastname: Howard
authors.forename: Y J
authors.initials: YJ
authors.lastname: Fei
authors.forename: M
authors.initials: M
authors.lastname: Aksoy
authors.forename: C
authors.initials: C
authors.lastname: Altay
authors.forename: A
authors.initials: A
authors.lastname: Gurgey
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D013789:Thalassemia / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D005914:Globins