Lesch-Nyhan syndrome is caused by a mutation in which gene?

• A. HPRT
• B. BRCA1
• C. CFTR
• D. TP53

Answer: (A)

Lesch-Nyhan syndrome results from a deficiency of the purine salvage enzyme HGPRT, caused by a mutation in the HPRT1 gene. This gene encodes hypoxanthine-guanine phosphoribosyltransferase, which normally salvages hypoxanthine and guanine into IMP and GMP using PRPP. When HGPRT is deficient, purines are not salvaged efficiently, leading to increased de novo purine synthesis and overproduction of uric acid. Clinically, this causes hyperuricemia with gout and uric acid stones, as well as neurological and behavioral abnormalities, often including self-injurious behavior. The HPRT1 gene is located on the X chromosome, so the condition is typically X-linked recessive, affecting males more often. The other genes listed are linked to completely different diseases (BRCA1 with breast/ovarian cancer risk, CFTR with cystic fibrosis, TP53 with various cancers), not Lesch-Nyhan.