The C-T substition in the distal CACCC box of the β-globin gene promoter is a common cause of silent β thalassaemia in the Italian population

M. S. Ristaldi, S. Murru, G. Loudianos, L. Casula, S. Porcu, D. Pigheddu, B. Fanni, G. V. Sciarratta, S. Agosti, M. I. Parodi, D. Leone, C. Camaschella, A. Serra, M. Pirastu, A. Cao

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Abstract

This paper describes four families of Italian descent in each of which the propositus had the clinical phenotype of thalassaemia intermedia, resulting from the compound heterozygous state for high HbA2 β thalassaemia and type I silen β thalassaemia. Direct sequencing on amplified DNA and/or oligonucleotide analysis detected, in all families but one, the compound heterozygous state for codon 39 nonsense mutation and the C-T substitution at position -101 in the distal CACCC box of the β-globin gene promoter (β(th-101)). Members of these families who are heterozygous for high HbA2 β thalassaemia showed the codon 39 nonsense mutation, while those with the clinical phenotype of silent β thalassaemia had the β(th-101) mutation. In the remaining family, the propositus and one of his siblings had the compound heterozygous state for a molecularly undefined high HbA2 β thalassaemia and the β(th-101) mutation in combination with the triple α globin gene arrangement. These patients showed a more severe thalassaemia intermedia like clinical phenotype as compared to those with the same β-globin genotype and a normal α-globin gene arrangement. In the families investigated the β(th-101) was always associated with haplotype I. A group of patients with thalassaemia intermedia from Southern Italy, either homozygous or heterozygous for haplotype I and in whom previous studies had failed to define the mutation in one of the β thalassaemia globin genes, were screened by oligonucleotide analysis for the presence of the β(th-101). Three out of nine were positive. These results indicate that the β(th-101) mutation is a common cause of the type I silent β thalassaemia phenotype in the Southern Italian population.

Original languageEnglish
Pages (from-to)480-486
Number of pages7
JournalBritish Journal of Haematology
Volume74
Issue number4
Publication statusPublished - 1990

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Thalassemia
Globins
beta-Thalassemia
Population
Genes
Phenotype
Mutation
Gene Order
Nonsense Codon
Codon
Oligonucleotides
Haplotypes
Italy
Siblings
Genotype
DNA

ASJC Scopus subject areas

  • Hematology

Cite this

Ristaldi, M. S., Murru, S., Loudianos, G., Casula, L., Porcu, S., Pigheddu, D., ... Cao, A. (1990). The C-T substition in the distal CACCC box of the β-globin gene promoter is a common cause of silent β thalassaemia in the Italian population. British Journal of Haematology, 74(4), 480-486.

The C-T substition in the distal CACCC box of the β-globin gene promoter is a common cause of silent β thalassaemia in the Italian population. / Ristaldi, M. S.; Murru, S.; Loudianos, G.; Casula, L.; Porcu, S.; Pigheddu, D.; Fanni, B.; Sciarratta, G. V.; Agosti, S.; Parodi, M. I.; Leone, D.; Camaschella, C.; Serra, A.; Pirastu, M.; Cao, A.

In: British Journal of Haematology, Vol. 74, No. 4, 1990, p. 480-486.

Research output: Contribution to journalArticle

Ristaldi, MS, Murru, S, Loudianos, G, Casula, L, Porcu, S, Pigheddu, D, Fanni, B, Sciarratta, GV, Agosti, S, Parodi, MI, Leone, D, Camaschella, C, Serra, A, Pirastu, M & Cao, A 1990, 'The C-T substition in the distal CACCC box of the β-globin gene promoter is a common cause of silent β thalassaemia in the Italian population', British Journal of Haematology, vol. 74, no. 4, pp. 480-486.
Ristaldi, M. S. ; Murru, S. ; Loudianos, G. ; Casula, L. ; Porcu, S. ; Pigheddu, D. ; Fanni, B. ; Sciarratta, G. V. ; Agosti, S. ; Parodi, M. I. ; Leone, D. ; Camaschella, C. ; Serra, A. ; Pirastu, M. ; Cao, A. / The C-T substition in the distal CACCC box of the β-globin gene promoter is a common cause of silent β thalassaemia in the Italian population. In: British Journal of Haematology. 1990 ; Vol. 74, No. 4. pp. 480-486.
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abstract = "This paper describes four families of Italian descent in each of which the propositus had the clinical phenotype of thalassaemia intermedia, resulting from the compound heterozygous state for high HbA2 β thalassaemia and type I silen β thalassaemia. Direct sequencing on amplified DNA and/or oligonucleotide analysis detected, in all families but one, the compound heterozygous state for codon 39 nonsense mutation and the C-T substitution at position -101 in the distal CACCC box of the β-globin gene promoter (β(th-101)). Members of these families who are heterozygous for high HbA2 β thalassaemia showed the codon 39 nonsense mutation, while those with the clinical phenotype of silent β thalassaemia had the β(th-101) mutation. In the remaining family, the propositus and one of his siblings had the compound heterozygous state for a molecularly undefined high HbA2 β thalassaemia and the β(th-101) mutation in combination with the triple α globin gene arrangement. These patients showed a more severe thalassaemia intermedia like clinical phenotype as compared to those with the same β-globin genotype and a normal α-globin gene arrangement. In the families investigated the β(th-101) was always associated with haplotype I. A group of patients with thalassaemia intermedia from Southern Italy, either homozygous or heterozygous for haplotype I and in whom previous studies had failed to define the mutation in one of the β thalassaemia globin genes, were screened by oligonucleotide analysis for the presence of the β(th-101). Three out of nine were positive. These results indicate that the β(th-101) mutation is a common cause of the type I silent β thalassaemia phenotype in the Southern Italian population.",
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T1 - The C-T substition in the distal CACCC box of the β-globin gene promoter is a common cause of silent β thalassaemia in the Italian population

AU - Ristaldi, M. S.

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AU - Loudianos, G.

AU - Casula, L.

AU - Porcu, S.

AU - Pigheddu, D.

AU - Fanni, B.

AU - Sciarratta, G. V.

AU - Agosti, S.

AU - Parodi, M. I.

AU - Leone, D.

AU - Camaschella, C.

AU - Serra, A.

AU - Pirastu, M.

AU - Cao, A.

PY - 1990

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N2 - This paper describes four families of Italian descent in each of which the propositus had the clinical phenotype of thalassaemia intermedia, resulting from the compound heterozygous state for high HbA2 β thalassaemia and type I silen β thalassaemia. Direct sequencing on amplified DNA and/or oligonucleotide analysis detected, in all families but one, the compound heterozygous state for codon 39 nonsense mutation and the C-T substitution at position -101 in the distal CACCC box of the β-globin gene promoter (β(th-101)). Members of these families who are heterozygous for high HbA2 β thalassaemia showed the codon 39 nonsense mutation, while those with the clinical phenotype of silent β thalassaemia had the β(th-101) mutation. In the remaining family, the propositus and one of his siblings had the compound heterozygous state for a molecularly undefined high HbA2 β thalassaemia and the β(th-101) mutation in combination with the triple α globin gene arrangement. These patients showed a more severe thalassaemia intermedia like clinical phenotype as compared to those with the same β-globin genotype and a normal α-globin gene arrangement. In the families investigated the β(th-101) was always associated with haplotype I. A group of patients with thalassaemia intermedia from Southern Italy, either homozygous or heterozygous for haplotype I and in whom previous studies had failed to define the mutation in one of the β thalassaemia globin genes, were screened by oligonucleotide analysis for the presence of the β(th-101). Three out of nine were positive. These results indicate that the β(th-101) mutation is a common cause of the type I silent β thalassaemia phenotype in the Southern Italian population.

AB - This paper describes four families of Italian descent in each of which the propositus had the clinical phenotype of thalassaemia intermedia, resulting from the compound heterozygous state for high HbA2 β thalassaemia and type I silen β thalassaemia. Direct sequencing on amplified DNA and/or oligonucleotide analysis detected, in all families but one, the compound heterozygous state for codon 39 nonsense mutation and the C-T substitution at position -101 in the distal CACCC box of the β-globin gene promoter (β(th-101)). Members of these families who are heterozygous for high HbA2 β thalassaemia showed the codon 39 nonsense mutation, while those with the clinical phenotype of silent β thalassaemia had the β(th-101) mutation. In the remaining family, the propositus and one of his siblings had the compound heterozygous state for a molecularly undefined high HbA2 β thalassaemia and the β(th-101) mutation in combination with the triple α globin gene arrangement. These patients showed a more severe thalassaemia intermedia like clinical phenotype as compared to those with the same β-globin genotype and a normal α-globin gene arrangement. In the families investigated the β(th-101) was always associated with haplotype I. A group of patients with thalassaemia intermedia from Southern Italy, either homozygous or heterozygous for haplotype I and in whom previous studies had failed to define the mutation in one of the β thalassaemia globin genes, were screened by oligonucleotide analysis for the presence of the β(th-101). Three out of nine were positive. These results indicate that the β(th-101) mutation is a common cause of the type I silent β thalassaemia phenotype in the Southern Italian population.

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