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Secondary Mutation (c.94_95delAG) in A −α3.7 Allele Associated with Hb H Disease in Two Unrelated African American Individuals Homozygous for the −α3.7 Deletion (−α3.7/−α3.7T)

Hb H disease is rarely seen in individuals of African descent although α-thalassemia (α-thal) is common in this population. Usually α-thal is due either to heterozygosity or homozygosity for the −α3.7 deletion in this population. We report Hb H disease that is caused by a frameshift mutation on one −α3.7 allele in two unrelated individuals homozygous for the −α3.7 deletion. These two cases highlight the importance of further investigation by direct sequencing of the –α3.7 allele when the thalassemic phenotype does not correlate with the genotype obtained by initial molecular testing.