Novel α-Thalassemia Deletion Identified in an Indian Infant with Hb H Disease.

We report the identification of a large deletion of the α-globin gene cluster, which removed both and and included the region from to on chromosome 16 (16p13.3). The α-thalassemia (α-thal) deletion was discovered in an Indian family residing in New Zealand. The proband was a 3-month-old female, who presented with a Hb H disease of unknown molecular origin. Routine hematology showed marked hypochromic microcytic anemia, with numerous Hb H inclusion bodies. In the absence of iron deficiency, there was a strong clinical suspicion of α-thal. On initial screening using a multiplex gap polymerase chain reaction (gap-PCR), only the common rightward deletion (-α) was detected. Investigation of the proband's mother and father revealed the mother was heterozygous for the -α deletion, while none of the seven most common pathogenic α-thal deletions were detected in the father. Multiplex ligation-dependent probe amplification (MLPA) was employed to detect the presence of a novel α-thal deletion in both the proband and her father. For the proband, the α-thal deletion in combination with the -α deletion, eliminated three copies of consistent with a clinical diagnosis of Hb H disease.