Balearic archipelago: three islands, three beta‐thalassemia population patterns

Abstract

López‐Escribano H, Parera MM, Guix P, Serra JM, Gutierrez A, Balsells D, Oliva‐Berini E, Castro JA, Ramon MM, Picornell A. Balearic archipelago: three islands, three beta‐thalassemia population patterns. The mutation spectrum of 175 β‐thalassemia (β‐thal) carriers, identified in pilot carrier screening on 22,713 individuals from Balearic Islands (Spain), is reported. The β0 CD39 (C>T) mutation is the most frequent (61.1%), followed by β+ IVS‐I‐110 (G>A) (12.0%), β+ IVS‐I‐6 (T>C) and β0 IVS‐1‐1 (G>A) (3.4% both) and eight other rare mutations (2.9–0.6%); with a distinct prevalence and distribution between islands. Minorca shows the highest prevalence in Iberian populations, with a single mutation, CD39 (C>T), present in most β‐thal carriers. Ibiza is the only Western Mediterranean population where the most frequent β‐thal mutation is IVS‐I‐110 (G>A). These results can be explained by a combination of historical–demographic characteristics together with evolutionary forces such as founder effect, genetic drift and probably selection by malaria. Knowledge of the mutational spectrum in the Balearic Islands will enable to optimize mutation detection strategy for genetic diagnosis of β‐thal in these islands.

Presence of the IVS-I-6-Mutated Allele in Beta-Thalassemia Major Patients Correlates with Extramedullary Hematopoiesis Incidence

“…The IVS-I-6 (T→C) mutation is one of the most common causes of β-thalassemia among individuals of Mediterranean and Middle Eastern ancestry [39,40]. Its high incidence has been reported among populations from Portugal [41]; Spain [42,43]; Albania [44]; the region of former Yugoslavia [45,46,47,48]; Greece [49,50,51,52]; Algeria [53]; Egypt [54]; Palestine [55,56]; Lebanon [57]; Syria [58,59]; Cyprus [60]; Turkey [61,62,63,64,65]; Saudi Arabia [66,67]; Iraq [68,69,70,71]; Iran [72,73,74]; and elsewhere. It results from a base substitution close to the 5′ splice junction, between exon I and intron I, and within a conserved consensus sequence, interfering with mRNA splicing and, consequently, reducing its efficiency.…”

Mismatch repair genes founder mutations and cancer susceptibility in Lynch syndrome

“…Founder mutations can cause recessive patterns of pathogenicity such as hemochromatosis , beta thalassemia , cystic fibrosis or xeroderma pigmentosum among others. In dominant predisposing diseases, founder mutations usually exist when the age of onset of the disease is past the reproductive age, so they are not eliminated because of reduced reproductive fitness.…”