β-Thalassemia mutations in subjects with borderline HbA₂ values

a pilot study in North India

Rangan, Aruna
Sharma, Prashant
Dadu, Tina
Saxena, Renu
Verma, Ishwar C.
Bhargava, Manorama

¹Department of Hematology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India
²Centre for Genetics, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, India

*Corresponding author: Dr. Aruna Rangan, Department of Hematology, 1st Floor, Super-speciality and Research Block, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi 110060, India Phone: 011-42252101, Fax: 011-42252148, E-mail: [email protected]

Received February 10, 2011; accepted August 3, 2011; previously published online September 6, 2011

Clinical Chemistry and Laboratory Medicine 49(12):p 2069-2072, December 2011.

Background

Interpreting hemoglobin high performance liquid chromatograms with borderline HbA₂ values is often problematic, especially in antenatal cases if the partner is a known thalassemia trait.

Methods

We tested for underlying β-thalassemia mutations in 25 subjects with borderline HbA₂ values (between 3.0%–4.0%). Amplification refractory mutation system (ARMS-PCR) was used to detect the five common Indian β-thalassemia mutations: (IVS-I-5 (G>C), IVS-I-1 (G>T), codons 8/9 (+G), codons 41/42 (-TTCT) and 619 bp deletion). β-Globin gene sequencing was performed if no mutation was detected.

Results

A β-globin gene defect was identified in 8 (32%) of the 25 cases with HbA₂ levels ranging from 3.5%–3.9%. ARMS-PCR revealed IVS-I-5 (G>C) in three, 619 bp deletion in two and codons 41/42 (-TTCT) in one case. Two cases had CAP +1 (A>C) mutation on gene sequencing. IVS-I-1 (G>T) and codons 8/9 (+G) were not found in this small cohort.

Conclusions