AnAluElement-Mediated 28.5 kb α-Thalassemia Deletion Found in a Chinese Family

Abstract

Over 95.0% of the α-thalassemia (α-thal) cases in southern China are caused by large deletions involving the α-globin gene. Here, we describe the molecular characterization of a novel 28.5 kb deletion that eliminated one of the duplicated α-globin genes in a Chinese family. The deletion breakpoint fragment involved Alu repeat sequences, suggesting a homologous recombination event. Phenotypic analysis on the heterozygous carrier of this deletion revealed that it leads to a very mild phenotype. Because of a 25.0% risk of Hb H (β4) disease in the offspring when in combination with another α(0)-thal allele, we should not ignore screening the deletion in prenatal diagnosis in order to decrease reproductive risk.

Transposable Elements and Human Diseases: Mechanisms and Implication in the Response to Environmental Pollutants

“…Deletions involving Alu repeats have been observed in the β-globin gene cluster, which includes the γ-, δ-, and β-globin genes [ 84 , 85 ]. For example, in an individual with hereditary persistence of fetal hemoglobin (γ-globin), the β-globin cluster has a large 48.5-kb deletion downstream of the β-globin gene, and the 5′ breakpoint of the deletion is in a 3′ Alu element of the Aγ-globin gene, one of the two genes (Aγ and Gγ) of fetal globin.…”

“…The following are examples of recombination events that lead to α-thalassemia, an inherited hemoglobin disease characterized by quantitative reduction of the α-globin chain and anemia. In one family of patients with α-thalassemia, there was a 28.5-kb deletion involving Alu repeats that eliminated one of the duplicated α-globin genes [ 85 ]. In another patient family, an 8.2 kb deletion in the α-globin gene cluster was found.…”

Mobile Elements in the Human Genome: Implications for Disease

“…of Alu repeats ( Table 1) In addition to cancer, several human diseases can be attributed to Alu-mediated 204 rearrangements ( Table 1) involving Alu repeats has been described that eliminated one of the duplicated α-globin 231 genes (Yu et al, 2014). A 33-kb α 0 -thalassaemia deletion encompassing the α-and ζ-globin 232 genes and pseudogenes has been observed in a Dutch family and this deletion appears 233 similar to a previously described one (Harteveld et al, 1997).…”