Hb Feilding [ß12(A9)Thr → Pro; HBB: c.37A>C]: a novel unstable ß-globin chain variant.

We report here a patient heterozygous for a previously unreported ß chain variant. A 72-year-old Caucasian female was found to have an abnormal hemoglobin (Hb) as an incidental finding following Hb A1C analysis. There was no family history of anemia or hemoglobinopathy. Her full blood count revealed a mild normochromic anemia with Hb 11.1 g/dL (range 11.5-15.0), mean corpuscular volume (MCV) 93.0 fL (range 80.0-100.0) and mean corpuscular Hb (MCH) 30.0 pg (range 27.0-32.0). Isopropanol stability tests and a variant Hb on high performance liquid chromatography (HPLC) comprizing 37.0% of the total Hb suggested an unstable Hb variant. Sanger sequencing of the ß-globin gene revealed a single base substitution, HBB: c.37A>C, causing the missense mutation ß12(A9)Thr → Pro in exon 1 of the HBB gene. This mutation changes the threonine residue at position 12(A9) to a proline in the ß-globin chain. We propose that this variant be called Hb Feilding after the town where the proband lived. Three dimensional modeling suggested that the disruption of the Hb structure was due to the introduction of a proline at helix A9 which caused distortion of the helical structure and resulted in reduced solubility.

Evaluation of an immunochromatographic strip test for alpha-thalassaemia screening.

INTRODUCTION: Hb H inclusion test (HbH-i) commonly used for α-thalassaemia screening is not standardised and is labour-intensive. This study evaluated a strip test based on immunochromatographic detection of Hb Bart's (ICT) for use as a routine screening test for α-thalassaemia screening in the clinical laboratory setting. METHODS: The performance characteristics of the ICT was determined by comparing the results of ICT and HbH-i on 67 patients, and the α-globin genotype on 47 of these patients who also had the molecular analysis. Specimen stability was tested on 16 specimens with the ICT repeated after 7 days of storage. The age of babies from which the ICT result becomes valid was determined on 49 samples with patient age ranged from 4 weeks to 12 months. RESULTS: The ICT had higher overall sensitivity of 76% compared to 24% for HbH-i in detecting carriers of α-thalassaemia mutations, and this is seen in all α-thalassaemia genotypes. The test could be carried out on specimens stored at 4°C for 7 days and gave valid results with no false positive from the age of 6 months onwards. It required no special technical expertise or equipment and gave the result in less than 5 minutes. CONCLUSION: The ICT is simple to perform, with higher sensitivity than HbH-i, and gives the result in a short time and at a lower cost. This can be used by clinical laboratories to replace HbH-i for α-thalassaemia detection.