Mutation analysis of β-thalassemia in East-Western Indian population: a recent molecular approach

Abstract

Background

β-Thalassemia is the most prevalent genetic disorder in India. Its traits and coinheritance vary from mild to severe conditions, resulting in thalassemia minor, intermediate, and major, depending upon many factors.

Purpose

The objective of this study was to identify the incidence of β-thalassemia traits, their coinheritance, and mutations, as well as to support the patients already diagnosed with β-thalassemia in East-Western Indian population for better management.

Patients and methods

Seventy-five referral cases for β-thalassemia were analyzed for various β-thalassemia traits, heterozygosity, and homozygosity conditions. Blood phenotypic parameters using cell counter and capillary electrophoresis were investigated. Analyses of eight common mutations of thalassemia in India were carried out using polymerase chain reaction-amplification refractory mutation system, end point polymerase chain reaction, and DNA sequencing methods.

Results

Of these (75) referral cases from East-Western Indian region, 68 were positive for β-thalassemia (90.67%). The majority of case types were of β-thalassemia minor (49, 65.33%), followed by HbE traits (6, 8.0%) and β-thalassemia major, including heterozygous and homozygous (5, 6.66%; 4, 5.33%) types and then HbE homozygous (2, 2.66%), as well as one each of the HbE/β-thalassemia and HbD/β-thalassemia (1, 1.34%) combination. Mutation analysis also revealed that the highest frequency of mutation was c.92+5G>C (41, 60.29%) followed by deletion 619bp (9, 13.23%) and c.79G>A (8, 11.76%) in our study group. Five cases (nos. 24, 27, 33, 58, and 71) exhibited coinheritance between β⁰/β⁺ (2), β⁰/β D (1), and c.124_127delTTCT/β⁺ or β⁰(2) affecting the Rajasthani and Gujarati populations in our study of the Western region of India.

Conclusion

We strongly recommend these Western populations for genetic screening before adopting reproductive technologies and interracial marital relations.

Keywords:

• β-thalassemia traits
• coinheritance
• hematogram
• capillary electrophoresis
• PCR-ARMS
• DNA sequencing
• mutation analysis
• East-Western India

Acknowledgments

The authors are thankful to all the staff including Clinicians of Supratech Micropath Laboratory, Ahmedabad, for their continuous assistance in this work. Parth S Shah, Nidhi D Shah, and Sandip C Shah are son, daughter-in-law, and father, respectively, who run this research institute.

Author contributions

Parth S Shah and Nidhi D Shah have contributed to writing results and discussion in the manuscript preparation when they visit India. Hari P Ray, Nikunj B Khatri, Ketan K Vaghasia, and Rutvik J Raval are involved in collection of blood from the patients after duly filled consent forms, blood analysis, DNA extraction, DNA sequencing, PCR-ARMS, end point PCR, and data analysis of 75 patients. Dr Sandip C Shah and Dr Mandava V Rao have contributed to preparation of reports after finalization of the results and preparation of the manuscript finally for submission to the journal. All authors contributed toward data analysis, drafting and critically revising the paper and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.