title: Phenotype of mutations in the promoter region of the β-globin gene.
abstract: BACKGROUND
  β+-Thalassaemia is characterised by reduced production of β chains, which decrease can be caused by mutations in the promoter region (CACCC or TATA box), and is classified as mild or silent depending on the extent of β-globin chain reduction. In both cases, homozygotes or compound heterozygotes for these mutations usually have thalassaemia intermedia. Frequently the diagnosis is made in adulthood or even in old age. A total of 37 alterations in the promoter region have been described so far.
  
  
  OBJECTIVE
  In this report we describe the mutations found in the promoter region of the β-globin gene in a single hospital in Madrid.
  
  
  METHODS
  Between 1998 and 2015, more than 9000 blood samples were analysed for full blood count and underwent haemoglobin electrophoresis and high performance liquid chromatography. Genetic analysis of the β and Gγ-globin genes was carried out by automatic sequencing and, in the case of α genes, by multiplex PCR.
  
  
  RESULTS
  35 samples showed mutation in the promoter region of the β-globin gene, with a total of six different mutations identified: one in the distal CACCC box, two in the proximal CACCC box, three in the ATA box.
  
  
  CONCLUSIONS
  Any alterations in the proximal CACCC and TATA boxes lead to a moderate decrease in synthesis of the β-globin chain, which has been demonstrated in cases of thalassaemia intermedia that have presented in the second decade of life with a moderate clinical course.
authors.affiliation: Servicio de Hematología, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Ropero
authors.affiliation: Servicio de Hematología, Hospital Universitario de Cruces, Bilbao, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Erquiaga
authors.affiliation: Servicio de Hematología, Hospital Universitario de Cruces, Bilbao, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Arrizabalaga
authors.affiliation: Servicio de Hematología, Hospital Universitario Marques de Valdecilla, Santander, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Pérez
authors.affiliation: Servicio de Hematología, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: de la Iglesia
authors.affiliation: Servicio de Análisis Clínicos, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Torrejón
authors.affiliation: Servicio de Pediatría, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Gil
authors.affiliation: Servicio de Pediatría, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
authors.forename: Cela
authors.initials: C
authors.lastname: Elena
authors.affiliation: Servicio de Hematología, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Tenorio
authors.affiliation: Servicio de Hematología, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Jorge M
authors.initials: JM
authors.lastname: Nieto
authors.affiliation: Servicio de Hematología, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Félix
authors.initials: F
authors.lastname: de la Fuente-Gonzalo
authors.affiliation: Servicio de Hematología, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Villegas
authors.affiliation: Servicio de Hematología, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Fernando-Ataúlfo
authors.initials: FA
authors.lastname: González Fernández
authors.affiliation: Servicio de Hematología, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013030:Spain; D055815:Young Adult; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D055544:beta-Globins
keywords: MOLECULAR GENETICS; SICKLE CELL DISEASE; THALASSAEMIA