Compound Heterozygote of Hb S (HBB: c.20A>T)/Hb Westdale (HBB: c.380_396delTGCAGGCTGCCTATCAG): Report of Four Cases from Odisha State, India

Abstract

We report four cases of compound heterozygotes for Hb S (HBB: c.20A>T) and a rare β⁰-thalassemia (β⁰-thal) mutation, Hb Westdale (HBB: c.380_396delTGCAGGCTGCCTATCAG), characterized by a 17 bp deletion between codons 126 to 131 in exon 3 of the β-globin gene of human hemoglobin (Hb) confirmed by direct β-globin gene sequencing. All four cases were from four unrelated families belonging to the Agharia caste, an endogamous ethnic community of the Sundargarh and Jharsuguda districts of Odisha State, India. Detailed observations indicated that all four cases of Hb S/Hb Westdale were clinically severe. On family screening, six family members were found to be heterozygous for Hb Westdale and were asymptomatic. Deletional α-thalassemia (α-thal) and XmnI polymorphism were studied for all the Hb Westdale cases. The Hb S/Hb Westdale cases had an early median age at onset of symptoms and presentation, more requirement of blood transfusions, splenomegaly and hepatomegaly and were found to be clinically more severe when compared with the Hb S-β-thal with IVS-I-5 (G>C) (HBB: c.92 + 5G>C) cases. Overall, the findings indicate that this rare and hitherto unreported compound heterozygosity of Hb S/Hb Westdale is a clinically significant hemoglobinopathy and its finding in a large endogamous community of Odisha State, India will have important implication in the epidemiology and understanding of the clinical spectrum of sickle cell disease in Indian context and prenatal diagnosis.

Keywords:

• α-Thalassemia (α -thal)
• β-globin gene sequencing
• Hb S/β -thalassemia (Hb S/β-thal)
• Hb S/Hb Westdale
• sickle cell disease
• XmnI polymorphism

Acknowledgments

The authors would like to thank the Director, V.S.S. Institute of Medical Sciences and Research, Burla, Sambalpur, Odisha (VIMSAR) and the Dean and Principal, VIMSAR for their kind support and necessary official approval. The authors also acknowledge the support of the Director, Anthropological Survey of India, Ministry of Culture, Government of India for sanctioning and supporting the collaboration program between the Odisha Sickle Cell Project (NHM, Odisha) and the Anthropological Survey of India, Head Office, Kolkata (Vide letter No. 18-22/PMI/2011, dated June 15 2013). The authors are indebted to the late Dr. Dilip Kumar Patel, Ex-Associate Professor, Department of Medicine, Veer Surendra Sai Medical College, Burla, Sambalpur, Odisha and Ex-Project Coordinator, Odisha Sickle Cell Project (NHM) for his inestimable contribution in this study.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.