Novel Alpha(0)-Thalassemia Deletion Identified In An Indian Infant With Hb H Disease

We report the identification of a large deletion of the alpha-globin gene cluster, which removed bothHBA2andHBA1and included the region fromHBZtoHBQ1on chromosome 16 (16p13.3). The alpha(0)-thalassemia (alpha(0)-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 alpha-thal. On initial screening using a multiplex gap polymerase chain reaction (gap-PCR), only the common rightward deletion (-alpha(3.7)) was detected. Investigation of the proband's mother and father revealed the mother was heterozygous for the -alpha(3.7)deletion, while none of the seven most common pathogenic alpha-thal deletions were detected in the father. Multiplex ligation-dependent probe amplification (MLPA) was employed to detect the presence of a novel alpha(0)-thal deletion in both the proband and her father. For the proband, the alpha(0)-thal deletion in combination with the -alpha(3.7)deletion, eliminated three copies ofHBAconsistent with a clinical diagnosis of Hb H disease.