Human HPRT1 gene and the Lesch–Nyhan disease: Substitution of alanine for glycine and inversely in the HGprt enzyme protein

ABSTRACT

Lesch–Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. The authors report three novel independent mutations in the coding region of the HPRT1 gene from genomic DNA of (a) a carrier sister of two male patients with LND: c.569G>C, p.G190A in exon 8; and (b) two LND affected male patients unrelated to her who had two mutations: c.648delC, p.Y216X, and c.653C>G, p.A218G in exon 9. Molecular analysis reveals the heterogeneity of genetic mutation of the HPRT1 gene responsible for the HGprt deficiency. It allows fast, accurate detection of carriers and genetic counseling.

KEYWORDS:

• Lesch—Nyhan disease
• HPRT1 gene
• HGprt enzyme
• mutation
• PCR
• sequencing

Acknowledgments

This work was supported by grants from the Lesch–Nyhan Syndrome Children's Research Foundation and the Harold A. and Madeline R. Jacobs Fund at The San Diego Foundation. We are grateful to the patients and their families for agreeing to participate in this study.