title: Identification of three new nucleotide substitutions in the β-globin gene: laboratoristic approach and impact on genetic counselling for beta-thalassaemia.
abstract: OBJECTIVE
  Over the past two decades, a wide range of available methods for DNA analysis have allowed us to identify defects in globin genes associated with haemoglobin disorders and to correlate specific mutations with phenotypic expression. The purpose of this study was to evaluate the nature of three new nucleotide changes, mutation or single nucleotide polymorphism, found in the beta-globin gene, to conduct an appropriate genetic counselling.
  
  
  METHODS
  We report the molecular study performed in three probands and their families, sampling during the screening programme conducted at the Laboratory for Molecular Prenatal Diagnosis of Hemoglobinopathies at Villa Sofia-Cervello Hospital in Palermo, Italy.
  
  
  RESULTS
  This work allowed us to report three new nucleotide substitutions of the β-globin gene: a substitution of the nucleotide 16 in the CAP site area (HBB: c.-35 A>G), a substitution of the nucleotide 478 in the second intron (HBB: c.316-373) in association with β-haemoglobin variant Hb G Copenhagen (HBB:c.142G>A) and a substitution of the nucleotide 1656 within the 3' UTR (HBB: c.*+182 G>A) in association with the 1393-bp deletion (NG_000007.3:g.70060_71452del1393).
  
  
  CONCLUSIONS
  The present work emphasizes the importance of reporting the observed nucleotide changes to the Haemoglobin Variant Database, especially in the case of new or rare undefined mutations, to facilitate the determination of their phenotypic expression and the possible interactions with known molecular defects and to formulate an appropriate genetic counselling for couples at risk.
authors.affiliation: Department of Haematology for Rare Diseases of Blood and Blood-forming Organs, Regional Reference Laboratory for Screening and Prenatal Diagnosis of Haemoglobinopathies, Villa Sofia-Cervello Hospital, Palermo, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Vinciguerra
authors.forename: Cristina
authors.initials: C
authors.lastname: Passarello
authors.forename: Filippo
authors.initials: F
authors.lastname: Leto
authors.forename: Filippo
authors.initials: F
authors.lastname: Cassarà
authors.forename: Monica
authors.initials: M
authors.lastname: Cannata
authors.forename: Aurelio
authors.initials: A
authors.lastname: Maggio
authors.forename: Antonino
authors.initials: A
authors.lastname: Giambona
mesh_terms: D000328:Adult; D001483:Base Sequence; D030541:Databases, Genetic; D005260:Female; D005817:Genetic Counseling / Q000941:ethics / Q000458:organization & administration; D005820:Genetic Testing; D005838:Genotype; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007438:Introns; D007558:Italy; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D006455:Hemoglobins, Abnormal; D055544:beta-Globins; C029521:hemoglobin G Copenhagen
keywords: Hb G Copenhagen; haemoglobin; polymorphism; β-globin gene