Variable haematological and clinical presentation of β-thalassaemia carriers and homozygotes with the Poly A (T→C) mutation in the Indian population.
OBJECTIVE
To study the varied clinical and haematological profile of β-thalassaemia homozygotes, compound heterozygotes and heterozygotes with the Poly A (T→C) mutation and its implication in prenatal diagnosis.


METHODS
Forty individuals were included in the study. Peripheral smear examination, complete blood count and haemoglobin analysis were carried out. β-thalassaemia mutation analysis was carried out by reverse-dot-blot hybridization, amplification refractory mutation system and DNA sequencing of the β-globin gene.


RESULTS
Five of the six β-thalassaemia homozygotes with the Poly A (T→C) mutation and five individuals who were compound heterozygous for the Poly A (T→C) mutation along with another common Indian β-thalassaemia mutation showed a severe β-thalassaemia major phenotype, while one individual presented as a thalassaemia intermedia. Majority of the 28 heterozygous individuals with this mutation showed borderline HbA₂ (mean HbA₂ = 3.7 ± 0.4%) levels as compared to individuals with common β-thalassaemia mutations (mean HbA₂ = 5.2 ± 1.4%). The Mean Corpuscular Volume (MCV) levels in individuals heterozygous for the Poly A (T→C) mutation (mean MCV 70.0 ± 5.2 fl) were significantly higher than in individuals with other common β-thalassaemia mutations (mean MCV 60.7 ± 7.7 fl) (P < 0.001).


CONCLUSIONS
It is important to identify these often silent carriers of β-thalassaemia for prenatal diagnosis as homozygotes have a severe disease.
National Institute of Immunohaematology, Indian Council of Medical Research, Parel, Mumbai, India.
Khushnooma
K
Italia
Pratibha
P
Sawant
Reema
R
Surve
Marukh
M
Wadia
Anita
A
Nadkarni
Kanjaksha
K
Ghosh
Roshan
R
Colah
D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006455:Hemoglobins, Abnormal / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D008297:Male; D017354:Point Mutation; D011061:Poly A / Q000235:genetics* / Q000378:metabolism; D055544:beta-Globins / Q000235:genetics* / Q000378:metabolism; D017086:beta-Thalassemia / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
D006455:Hemoglobins, Abnormal; D055544:beta-Globins; D011061:Poly A