**Question:** Mutation seen in Hartnup's disease:

A. p.Phe508del (cystic fibrosis transmembrane conductance regulator)
B. p.Tyr356X (cystic fibrosis transmembrane conductance regulator)
C. p.Leu292Pro (cystic fibrosis transmembrane conductance regulator)
D. p.Arg106Trp (cystic fibrosis transmembrane conductance regulator)

**Correct Answer:**

**Hartnup's Disease** is a rare autosomal recessive disorder affecting the transport of essential amino acids across the intestinal brush border membrane and renal tubules. The correct answer is:

**A. p.Phe508del (cystic fibrosis transmembrane conductance regulator)**

The correct mutation refers to a deletion of cytosine (ΔC) at position 711, resulting in a phenylalanine (Phe) to leucine (Leu) substitution at amino acid residue 508 in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. This mutation is associated with cystic fibrosis, not Hartnup's disease.

Hartnup's disease is caused by mutations in the **SLC9A9** gene, encoding the human neutral amino acid transporter (H+/Ala antiporter, HATS). The mutations typically result in the absence or reduced function of the HATS transporter, leading to the clinical manifestations observed in Hartnup's disease.

Hartnup's disease is characterized by:

1. **Pica: excessive consumption of non-nutritive substances (e.g., chalk, soil), often due to nutritional deficiency.**
2. **Urolithiasis: kidney stones composed of neutral amino acids.**
3. **Pica and urolithiasis are seen in early childhood.**
4. **Altered amino acid and neurotransmitter profiles in urine and blood.**

**Why other options are incorrect:**

**B. p.Tyr356X:** This mutation refers to a premature stop codon resulting in truncated CFTR protein. It is associated with cystic fibrosis, not Hartnup's disease.

**C. p.Leu292Pro:** This mutation also pertains to the CFTR gene and is associated with cystic fibrosis, not Hartnup's disease.

**D. p.Arg106Trp:** This mutation is associated with cystic fibrosis, not Hartnup's disease.

In conclusion, Hartnup's disease is due to mutations in the **SLC9A9** gene, while other options refer to mutations in the **CFTR gene** associated with cystic fibrosis. The correct mutation (A) causes a missense substitution leading to a loss of function, while the incorrect options result in a premature stop codon leading to a truncated protein.