Hemoglobin H disease due to a de novo mutation at the α2-globin gene and an inherited common α-thalassemia deletion found in a Chinese boy

Hemoglobin (Hb) H disease is a moderate form of α-thalassemia resulting from various genetic defects. A novel frameshift mutation cd 43/44(− C) at the α2-globin gene was identified in a Chinese boy with hemoglobin H disease by sequencing. The proband's mother carries a common α-thalassemia deletion while his father was normal both in the hematological phenotype and α-globin genotype, which suggested that it occurred as a de novo mutation. Molecular studies revealed a compound heterozygote for the Southeast Asian α-thalassemia deletion and this novel spontaneous mutation (−/αTα) and the patient exhibited the clinical manifestation of classic hemoglobin H disease. Based on the results of excluding the possibility of a somatic mosaicism of a point mutation in the α2-globin gene, we progress that this de novo single-base deletion should have arisen during the spermatogenic process or earlier embryonic stage. The present study provides information in determining a supplementary model of inheritance for α-thalassemia, which should be useful in genetic counseling.