Origin of the Frameshift Codons 41 42 (-TCTT) Mutation in the First Cases Described in the Spanish Population

• Published in: Hemoglobin 2008-01, Vol.32 (5), p.513-519
• Main Authors: Ropero, Paloma, de la Iglesia, Silvia, Calvo-Villas, Jose M., Ataúlfo González, Fernando, Paúl, Rosa, Villegas, Ana
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Alleles; beta-Thalassemia - genetics; Codon - genetics; Female; Frameshift codons (FSC) 41/42 mutation; Frameshift Mutation; Genotype; Haplotypes; Humans; Male; Rare mutation in the Spanish population; Spain
• ISSN: 0363-0269; 1532-432X
• DOI: 10.1080/03630260802341968

Thalassemias are hereditary anemias. In β-thalassemia (β-thal), β-globin synthesis is either deficient or absent. A high incidence of β-thal is found in populations of Mediterranean and African origin. Smaller, but significant concentrations of β-thal are present throughout the Middle East, India, Pakistan and China, while sporadic cases have been reported in most ethnic groups. Over 200 β-thal mutations have been described so far. But each population group displays its own mutations. In Spain, as in other countries of the Mediterranean region, the most often seen mutations are codon 39 (C > T); IVS-I-1 (G > A); IVS-I-6 (T > C) and IVS-I-110 (G > A). However, a large number of rarer alleles have been observed both in Spain and other populations. The frameshift codons (FSC) 41 CD42 (-TCTT) mutation is a rather common allele in individuals of Chinese origin, but rare in the Mediterranean region, although, it has been recorded in East Asian populations. We describe the first eight Spanish patients displaying the FSC 41 42 mutation. This mutation was initially detected with a real-time polymerase chain reaction (PCR) method on a LightCycler™, using a probe designed to detect mutations in codons 37 and 39, and subsequently specifically characterized by automatic sequencing. The haplotype found in our patients suggested that this mutation has not arisen independently in our population but must be taken into account when identifying most β-thal mutations.