title: Molecular analysis of complex cases of alpha- and beta-thalassemia in Mexican mestizo patients with microcytosis and hypochromia reveals two novel alpha(0) -thalassemia deletions - -(Mex1) and - -(Mex2).
abstract: BACKGROUND
  Alpha-thalassemia (α-thal) is a common monogenic disorder worldwide. In mixed ethnic populations, α-thal and beta-thalassemia (β-thal) can be expected, sometimes giving complex phenotypes, which without molecular analysis are not easily explained. We performed the molecular identification of α- and β-thal alleles in 51 Mexican patients with microcytosis, hypochromia, and normal or low levels of HbA2 .
  
  
  METHODS
  Common deletional alleles (-α(3.7) , -α(4.2) , - -(SEA) , - -(MED) , - -(FIL) , - -(THAI) , -α(20.5) ) and α-triplication were studied by gap-PCR and nondeletional alleles (α(IVSI) ((-5nt)) , α2 (NcoI) , α1 (NcoI) ) by ARMS. β-thal alleles Cd39 (C>T), IVS1:1 (G>A), IVS1:110 (G>A), and Spanish δβ-thal were also investigated. DNA sequencing was performed on HBA2, HBA1, and HBB genes. Negative samples were subjected to MLPA.
  
  
  RESULTS
  In 35 subjects, we identified the mutations, -α(3.7) , - -(SEA) , - -(FIL) , α(IVSI) ((-5nt)) , and ααα(anti3.7) and two novel deletion alleles - -(Mex1) (6.8-8.9 kb) and - -(Mex2) (77.6-135.7 kb). Four individuals also had a β-thal allele (Cd39/IVS1:110). No α-thal alleles were observed in 16 subjects, but three had a β-thal mutation Cd39, IVS1:110, and Spanish δβ-thal.
  
  
  CONCLUSIONS
  α-thal is relatively common in Mexican patients, the combination with β-thal is sometimes unexpected, and this underlines the importance of performing molecular analysis for both α- and β-genes defects in patients showing microcytic hypochromic anemia.
authors.affiliation: Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: E I
authors.initials: EI
authors.lastname: de-la-Cruz-Salcedo
authors.affiliation: Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: B
authors.initials: B
authors.lastname: Ibarra
authors.affiliation: Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.|División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico.
authors.forename: L C
authors.initials: LC
authors.lastname: Rizo-de-la-Torre
authors.affiliation: Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.|División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico.
authors.forename: J Y
authors.initials: JY
authors.lastname: Sánchez-López
authors.affiliation: Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: González-Mercado
authors.affiliation: Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C L
authors.initials: CL
authors.lastname: Harteveld
authors.affiliation: Doctorado en Genética Humana, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico. javier_perea_diaz@yahoo.com.mx.|División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadalajara, Jalisco, Mexico. javier_perea_diaz@yahoo.com.mx.
authors.forename: F J
authors.initials: FJ
authors.lastname: Perea-Díaz
mesh_terms: D000483:Alleles; D000747:Anemia, Hypochromic / Q000235:genetics*; D001483:Base Sequence; D005260:Female; D006442:Glycated Hemoglobin / Q000235:genetics*; D006455:Hemoglobins, Abnormal / Q000235:genetics*; D006801:Humans; D008297:Male; D008800:Mexico; D017384:Sequence Deletion; D017085:alpha-Thalassemia / Q000235:genetics*; D017086:beta-Thalassemia / Q000235:genetics*
chemical_list: D006442:Glycated Hemoglobin; D006455:Hemoglobins, Abnormal
keywords: alpha-globin deletion; complex α- and β-thalassemia genotypes; microcytosis