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?

Question

Accepted Answer

C. IVS-1 position 5 (G→A). ## 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.

Answer

A. Codon 8/9 (+G)

Answer

B. Codon 26 (A→G)

Answer

D. Codon 39 (C→T)

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

Mechanism

Geographic and Ethnic Distribution

Why This Matters for NEET PG

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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