title: Variable presentation of HB H disease due to homozygosity for the rare polyadenylation signal A T(Indian) (AATAAA>AATA- -) mutation in four Indian families.
abstract: 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) T(Indian) (AATAAA>AATA-) mutation. This mutation has been seen in Eastern India but not from Maharashtra and Uttar Pradesh where our patients originated.
authors.affiliation: National Institute of Immunohaematology ICMR, King Edward Memorial Hospital Campus, Mumbai, India.
authors.forename: Sona B
authors.initials: SB
authors.lastname: Nair
authors.forename: Anita H
authors.initials: AH
authors.lastname: Nadkarni
authors.forename: Kanjaksha
authors.initials: K
authors.lastname: Ghosh
authors.forename: Roshan B
authors.initials: RB
authors.lastname: Colah
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007194:India; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D026723:Polyadenylation; D017384:Sequence Deletion; D012720:Severity of Illness Index; D055542:alpha-Globins / Q000235:genetics*; D017085:alpha-Thalassemia / Q000235:genetics* / Q000503:physiopathology
chemical_list: D055542:alpha-Globins