title: Association in cis of the mutations +20 (C>T) in the 5' untranslated region and IVS-II-745 (C>G) on the β-globin gene.
abstract: In the 5' untranslated region (5'UTR), which is transcribed but not translated and is involved in posttranscriptional regulation of the gene promoting and stabilizing the mRNA translation, several mutations associated with mild β-thalassemia (β-thal) have been described. One of these, the +20 (C>T) mutation, is described in the HbVar database as a mutation responsible for β(+)-thal. In heterozygote cases, it gives rise to a phenotype of β-thal minor and β-thal intermediate (β-TI) when the mutation is associated with β(+) IVS-II-745 (C>G). To clarify if this mutation is responsible for β(+)-thal, we studied nine cases where we found an association of the +20 and IVS-II-745 mutations. All patients were carriers of four α genes. Three patients carried β-thal major (β-TM), two were compound heterozygotes for IVS-II-745 and codon 8 (-AA) or codon 39 (C>T), and the third was homozygous for IVS-II-745; all had the +20 mutation in the 5'UTR. The remaining patients showed the mutation IVS-II-745 associated with a replacement of C>T at nucleotide (nt) +20 of the 5'UTR. Contrary to reports in the HbVar database, the +20 mutation should be considered as an innocuous single nt polymorphism associated with the IVS-II-745 mutation in cis.
authors: Servicio de Hematología, Hospital Clínico San Carlos de Madrid, Madrid, Spain. propero.hcsc@salud.madrid.org
authors: Paloma
authors: P
authors: Ropero
authors: Fernando A
authors: FA
authors: González
authors: Elena
authors: E
authors: Cela
authors: Cristina
authors: C
authors: Beléndez
authors: Aurea
authors: A
authors: Cervera
authors: Jorge
authors: J
authors: Martínez-Nieto
authors: Félix
authors: F
authors: de la Fuente-Gonzalo
authors: Lara
authors: L
authors: Vinuesa
authors: Ana
authors: A
authors: Villegas
authors: Joaquín
authors: J
authors: Díaz-Mediavilla
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000328:Adult; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult; D055544:beta-Globins / Q000235:genetics*; D017086:beta-Thalassemia / Q000175:diagnosis / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D055544:beta-Globins