Novel Mutations in the Human HPRT Gene

Abstract

Inherited mutation of a purine salvage enzyme, hypoxanthine guanine phosphoribosyltransferase (HPRT), gives rise to Lesch-Nyhan Syndrome (LNS) or HPRT-related gout. Here, we report five novel independent mutations in the coding region of the HPRT gene from five unrelated male patients manifesting different clinical phenotypes associated with LNS: exon 2: c.133A > G, p.45R > G; c.35A > C, p.12D > A; c.88delG; exon 7: c.530A > T, p.177D > V; and c.318 + 1G > C: IVS3 + 1G > C splice site mutation.

Keywords:

• Lesch-Nyhan Syndrome
• HPRT
• mutation, PCR
• sequencing

Acknowledgments

This work was supported by a grant from the Lesch-Nyhan Syndrome Children's Research Foundation. The authors are grateful to the patients and their families for agreeing to participate in this study.

Notes

^a HPRT activity is the mean of the three determinations and is expressed in nmol/hr/spot. The normal range values are between 10 to 24 nmol/hr/spot.

^b APRT activity is the mean of the three determinations and is expressed in nmol/hr/spot. The normal range values are between 0.5 to 7 nmol/hr/spot.

^c cDNA mutation numbering is based on GenBank NM_000194.2 with +1 as A of the ATG start codon.

^a Exon-flaking oligonucleotide primer sequences numbering is based on GenBank Accession No. M26434.

^a http://genetics.bwh.harvard.edu/pph/

^b http://sift.jcvi.org/