Variable Presentation of HB H Disease Due to Homozygosity for the Rare Polyadenylation Signal A TIndian (AATA AA>AATA- -) Mutation in Four Indian Families.

The aim of this study was to identify the molecular defects leading to the variable clinical and hematological presentation of four patients with Hb H disease. Investigations included a complete blood count, high performance liquid chromatography (HPLC) analyses, cellulose acetate electrophoresis (pH 8.9), heat stability test, α genotyping by multiplex gap polymerase chain reaction (gap-PCR) to screen for the eight common α-globin gene deletions and DNA sequencing to detect the other deletional and nondeletional α-globin gene mutations. Two patients aged 15 and 5.5 years had a mild clinical presentation. The first patient aged 3 years had a severe presentation requiring regular transfusions. This patient also had an enlarged spleen and had to undergo splenectomy. The third patient, aged 5 years, also had severe anemia, had been transfused once and had a spleen of 4.5 cms. The hemoglobin (Hb) levels in the four patients ranged from 4.2 to 8.2 g/dL and they all had reticulocytosis (10.0 to 31.0%). Cellulose acetate electrophoresis at pH 8.9 showed a fast moving band that ranged from 18.0 to 25.9%. All the four patients were homozygous for the polyadenylation signal A (polyA) TIndian (AATAAA>AATA-) mutation. This mutation has been seen in Eastern India but not from Maharashtra and Uttar Pradesh where our patients originated. [ABSTRACT FROM AUTHOR]