Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 1342-1347 |
| Number of pages | 6 |
| Journal | Blood |
| Volume | 77 |
| Issue number | 6 |
| Publication status | Published - Mar 15 1991 |
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ASJC Scopus subject areas
- Hematology
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Molecular characterization of β-thalassemia intermedia in patients of Italian descent and identification of three novel β-thalassemia mutations. / Murru, S.; Loudianos, G.; Deiana, M.; Camaschella, C.; Sciarratta, G. V.; Agosti, S.; Parodi, M. I.; Cerruti, P.; Cao, A.; Pirastu, M.
In: Blood, Vol. 77, No. 6, 15.03.1991, p. 1342-1347.Research output: Contribution to journal › Article
}
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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UR - http://www.scopus.com/inward/citedby.url?scp=0025762515&partnerID=8YFLogxK
M3 - Article
C2 - 2001456
AN - SCOPUS:0025762515
VL - 77
SP - 1342
EP - 1347
JO - Blood
JF - Blood
SN - 0006-4971
IS - 6
ER -