TY - JOUR
T1 - Molecular characterization of β-thalassemia intermedia in patients of Italian descent and identification of three novel β-thalassemia mutations
AU - Murru, S.
AU - Loudianos, G.
AU - Deiana, M.
AU - Camaschella, C.
AU - Sciarratta, G. V.
AU - Agosti, S.
AU - Parodi, M. I.
AU - Cerruti, P.
AU - Cao, A.
AU - Pirastu, M.
PY - 1991/3/15
Y1 - 1991/3/15
N2 - In this study, we have defined by dot-blot analysis with allelic specific oligonucleotide probes or direct sequencing on amplified DNA the β-thalassemia mutations in a large group of patients (23) of Italian descent with thalassemia intermedia. These patients had one parent with either the silent β-thalassemia carrier phenotype or borderline-normal hemoglobin A2 (HbA2) levels (2.5% to 3.5%). Nearly all were genetic compounds for a severe β-thalassemia mutation and a β-thalassemia mutation associated with high residual output of β-globin chains (β+ intervening sequence [IVS]-I-nt6, β-87, β-101), indicating that inheritance of a mild β-thalassemia allele, even in a single dose, is the most common molecular mechanism producing thalassemia intermedia in the Italian population. In three cases, in whom we failed to define by dot-blot analysis the mutations, we sequenced the β+globin gene and found three novel β-thalassemia mutations, which are certainly very rare because they have been hitherto detected solely in a single patient. These mutations consist of: (1) a T-A substitution at position 2 of IVS-I, in a patient compound heterozygote for this mutation and the -87 promoter mutation; (2) a G-C substitution at position 844 of IVS-II, in a patient heterozygous for this mutation who showed normal sequences at the in trans β-globin gene (The reason for the presence of clinical manifestations in a β-thalassemia heterozygote has not been defined.); and (3) a deletion of one nucleotide (-T) at codon 126, resulting in a frameshift and readthrough of the 5 untranslated region and most likely producing an elongated Hb molecule of 156 amino acid residues, in a patient heterozygous for this mutation with normal β-globin gene sequences at the other locus.
AB - In this study, we have defined by dot-blot analysis with allelic specific oligonucleotide probes or direct sequencing on amplified DNA the β-thalassemia mutations in a large group of patients (23) of Italian descent with thalassemia intermedia. These patients had one parent with either the silent β-thalassemia carrier phenotype or borderline-normal hemoglobin A2 (HbA2) levels (2.5% to 3.5%). Nearly all were genetic compounds for a severe β-thalassemia mutation and a β-thalassemia mutation associated with high residual output of β-globin chains (β+ intervening sequence [IVS]-I-nt6, β-87, β-101), indicating that inheritance of a mild β-thalassemia allele, even in a single dose, is the most common molecular mechanism producing thalassemia intermedia in the Italian population. In three cases, in whom we failed to define by dot-blot analysis the mutations, we sequenced the β+globin gene and found three novel β-thalassemia mutations, which are certainly very rare because they have been hitherto detected solely in a single patient. These mutations consist of: (1) a T-A substitution at position 2 of IVS-I, in a patient compound heterozygote for this mutation and the -87 promoter mutation; (2) a G-C substitution at position 844 of IVS-II, in a patient heterozygous for this mutation who showed normal sequences at the in trans β-globin gene (The reason for the presence of clinical manifestations in a β-thalassemia heterozygote has not been defined.); and (3) a deletion of one nucleotide (-T) at codon 126, resulting in a frameshift and readthrough of the 5 untranslated region and most likely producing an elongated Hb molecule of 156 amino acid residues, in a patient heterozygous for this mutation with normal β-globin gene sequences at the other locus.
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M3 - Article
C2 - 2001456
AN - SCOPUS:0025762515
VL - 77
SP - 1342
EP - 1347
JO - Blood
JF - Blood
SN - 0006-4971
IS - 6
ER -