Which gene is mutated in Lesch-Nyhan syndrome?

Which gene is mutated in Lesch-Nyhan syndrome?

• A. BRCA1
• B. HPRT gene (hypoxanthine-guanine phosphoribosyltransferase)
• C. CFTR
• D. APOE

Answer: (B)

Lesch-Nyhan syndrome arises from deficiency of HGPRT, caused by mutations in the HPRT1 gene on the X chromosome. HGPRT is part of the purine salvage pathway, reclaiming hypoxanthine and guanine to form IMP and GMP. When this enzyme is deficient, purine breakdown increases and uric acid builds up, leading to hyperuricemia and the distinctive neurobehavioral symptoms of the condition. The other genes listed are associated with unrelated processes—BRCA1 with DNA repair and cancer risk, CFTR with cystic fibrosis, APOE with lipid transport and Alzheimer’s risk—so they do not cause Lesch-Nyhan.

Lesch-Nyhan syndrome arises from deficiency of HGPRT, caused by mutations in the HPRT1 gene on the X chromosome. HGPRT is part of the purine salvage pathway, reclaiming hypoxanthine and guanine to form IMP and GMP. When this enzyme is deficient, purine breakdown increases and uric acid builds up, leading to hyperuricemia and the distinctive neurobehavioral symptoms of the condition. The other genes listed are associated with unrelated processes—BRCA1 with DNA repair and cancer risk, CFTR with cystic fibrosis, APOE with lipid transport and Alzheimer’s risk—so they do not cause Lesch-Nyhan.