Thalassaemia intermedia caused by coinheritance of a β-thalassaemia mutation and a de novo duplication of α-globin genes in the paternal allele.

Next generation sequencing identified a de novo, 204 kb, tandem duplication (αααα204 ) in the α-globin gene cluster of a Chinese thalassaemia intermedia patient. Haplotype analysis showed that the duplicated chromosome was of paternal origin. Molecular analysis of genomic DNA from the patient's lymphocytes, hair follicles, buccal mucosa cells, his father's lymphocytes and sperm cells excluded the possibility of somatic or germinal mosaicism. The analysis also indicated that this duplication arose during spermatogenesis. The microhomology in the breakpoint was found and suggested that this duplication could be formed by a coupled homologous and non-homologous recombination mechanism.