A 5-year-old child from Tamil Nadu presents with severe hemolytic anemia, hepatosplenomegaly, and bone deformities. Hemoglobin electrophoresis shows absence of β-globin chains. What is the most common β-globin gene mutation in Indian patients with β-thalassemia major?

Explanation

## Most Common β-Globin Mutation in Indian Thalassemia **Key Point:** The IVS-1 position 5 (G→A) mutation is the single most common β-globin gene defect in Indian patients with β-thalassemia major, accounting for approximately 30–40% of cases in India. ### Mechanism This mutation occurs in the invariant splice site of intron 1 (IVS-1) of the β-globin gene, disrupting normal mRNA splicing and leading to absent or severely reduced β-globin chain synthesis. ### Geographic and Ethnic Distribution | Mutation | Frequency in India | Phenotype | Geographic Clustering | |----------|-------------------|-----------|----------------------| | IVS-1 pos 5 (G→A) | 30–40% | β-thalassemia major | Pan-Indian, especially South | | Codon 26 (A→G) | 10–15% | β-thalassemia major | North India | | Codon 8/9 (+G) | 8–10% | β-thalassemia major | Scattered | | Codon 39 (C→T) | 5–8% | β-thalassemia major | Mediterranean, rare in India | **High-Yield:** IVS-1 pos 5 (G→A) is the **single most frequent mutation** in Indian populations and must be the first answer choice when asked about the commonest β-thalassemia mutation in India. **Clinical Pearl:** Patients homozygous for IVS-1 pos 5 typically present with severe β-thalassemia major requiring regular transfusions, consistent with the clinical presentation in this case. ### Why This Matters for NEET PG Indian hematology exams frequently test geographic variation in genetic mutations. The IVS-1 pos 5 mutation is the prototypical "Indian thalassemia mutation" and appears in multiple exam formats.