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.
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.
Gonzalez-Redondo
J M
JM
Department of Cell and Molecular Biology, College of Georgia, Augusta.
Stoming
T A
TA
Kutlar
A
A
Kutlar
F
F
Lanclos
K D
KD
Howard
E F
EF
Fei
Y J
YJ
Aksoy
M
M
Altay
C
C
Gurgey
A
A
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
D012333:RNA, Messenger; D005914:Globins