Variable presentation of HB H disease due to homozygosity for the rare polyadenylation signal A T(Indian) (AATAAA>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 (p...

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Bibliographic Details
Published in:Hemoglobin 2013, Vol.37 (3), p.277-284
Main Authors: Nair, Sona B, Nadkarni, Anita H, Ghosh, Kanjaksha, Colah, Roshan B
Format: Article
Language:English
Subjects:
Adolescent
Adult
alpha-Globins - genetics
alpha-Thalassemia - genetics
alpha-Thalassemia - physiopathology
Base Sequence
Child
Child, Preschool
Female
Genetic Heterogeneity
Genotype
Homozygote
Humans
India
Male
Molecular Sequence Data
Pedigree
Phenotype
Polyadenylation
Sequence Deletion
Severity of Illness Index
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Summary: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.
ISSN:1532-432X
DOI:10.3109/03630269.2013.774284