title: Co-heredity of silent CAP + 1570 T>C (HBB:c*96T>C) defect and severe β-thal mutation: a cause of mild β-thalassemia intermedia.
abstract: BACKGROUND
  During an intensive screening program aimed at identifying the healthy carriers of thalassemia and the couples at risk of bearing an affected fetus, a rare single nucleotide variation (SNV), CAP + 1570 T > C (HBB:c*96T > C), located 12 nucleotides upstream of the polyadenylation signal in 3'UTR of the beta globin gene was identified. It was previously reported as a β+ thalassemia mutation and later as a plain polymorphism.
  
  
  METHODS
  Genotype identification of globin gene mutations was carried out using sequencing analysis, GAP-PCR, and MLPA methods.
  
  
  RESULTS
  CAP + 1570 T > C (HBB:c*96T > C) was found in 39 heterozygotes, in one case in homozygous state and in thirteen cases of co-inheritance of this nucleotide substitution with other mutations in globin genes. Carriers of this mutation showed a 'silent' phenotype without appreciable microcytosis and hypochromia, so they cannot be differentiated from noncarrier individuals. Compound heterozygotes for this mutation and severe β-thal mutations showed a variable phenotype ranging from β-thal carrier to mild form of β-thalassemia intermedia, revealing new aspects and allowing to better understand the clinical implications of this nucleotide substitution that can be classified as a silent β-thalassemic defect.
  
  
  CONCLUSIONS
  Data reported in this study indicate the need of investigating partner of β-thalassemia carrier by complete sequencing analysis of β-globin gene and of providing an appropriate genetic counseling for couples at risk undergoing prenatal diagnosis.
authors.affiliation: Department of Hematology for Rare Diseases of Blood and Blood-Forming Organs, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital, Palermo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Vinciguerra
authors.affiliation: Department of Hematology for Rare Diseases of Blood and Blood-Forming Organs, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital, Palermo, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Passarello
authors.affiliation: Department of Hematology for Rare Diseases of Blood and Blood-Forming Organs, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital, Palermo, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cassarà
authors.affiliation: Department of Hematology for Rare Diseases of Blood and Blood-Forming Organs, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital, Palermo, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Leto
authors.affiliation: Department of Hematology for Rare Diseases of Blood and Blood-Forming Organs, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital, Palermo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Cannata
authors.affiliation: Department of Hematology for Rare Diseases of Blood and Blood-Forming Organs, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital, Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Calvaruso
authors.affiliation: Department of Hematology for Rare Diseases of Blood and Blood-Forming Organs, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital, Palermo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Di Maggio
authors.affiliation: Department of Hematology for Rare Diseases of Blood and Blood-Forming Organs, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital, Palermo, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Renda
authors.affiliation: Department of Hematology for Rare Diseases of Blood and Blood-Forming Organs, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Maggio
authors.affiliation: Department of Hematology for Rare Diseases of Blood and Blood-Forming Organs, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Hemoglobinopathies, Villa Sofia-Cervello Hospital, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Giambona
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000483:Alleles; D004252:DNA Mutational Analysis; D004909:Erythrocyte Indices; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012720:Severity of Illness Index; D000069456:Silent Mutation; D017085:alpha-Thalassemia / Q000235:genetics; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D055544:beta-Globins
keywords: 3'UTR β-globin gene mutation; Hemoglobinopathies; genetic counseling; screening program; thalassemia intermedia