A Novel 31.1 kb α-Thalassemia Deletion (– –^MEX3) Found in a Mexican Family

Abstract

α-Thalassemia (α-thal), a genetic disease characterized by microcytosis, hypochromia and anemia, is predominantly caused by deletions of the α-globin genes, HBA2 and HBA1. In this study, we describe a novel 31.1 kb α-thal deletion, – –^MEX3 (NC_000016.10: g.151479_182582del), observed in a Mexican family, probably originated from non homologous recombination between two Alu sequences; the 5′ Alu element has been involved in at least two other α-thal deletions [– –^FIL (NG_000006.1: g.11684_43534del) and – –^KOL] and possesses a core homologous sequence next to the – –^MEX3 breakpoint. In addition, a 286 bp insertion in an Alu sequence downstream to the – –^MEX3 3′ breakpoint was found in the studied family, – –^FIL carriers, and healthy subjects, suggesting a common genetic variation in the Mexican population. We highlight the involvement of Alu elements and their core sequence in the origin of deletions in the α-globin gene cluster, and the importance of characterizing rare mutations, to better understand DNA rearrangement origins.

Keywords:

• Alu sequences
• α-thalassemia (α-thal)
• Mexico
• novel deletion

Acknowledgments

We thank María T. Magaña-Torres and Ana R. Jaloma-Cruz (División de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social, Guadaljara, Jalisco, México) for their support in the DNA sequencing and MLPA techniques, respectively.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.