Five independent mutations in the hypoxanthine guanine phosphoribosyltransferase 
(HPRT) gene were identified in a partially HPRT deficient patient with gout and 
in four Lesch-Nyhan patients. Using the polymerase chain reaction (PCR) 
technique coupled with direct sequencing, the nucleotide sequences of the entire 
HPRT coding region amplified from the cDNA and also of each exon amplified form 
the genomic DNA were analyzed. Three independent point mutations in the coding 
region were detected in the partially HPRT deficient patient (Case 1) and in two 
Lesch-Nyhan patients (Case 2 and 3), resulting in single amino acid 
substitutions. The family study of Case 3, utilizing a PvuII restriction site 
created in the mutant gene, indicated that the mother was a heterozygote, and a 
sister and a fetal brother had inherited the normal HPRT gene from the mother. 
In two other mutants causing Lesch-Nyhan syndrome, a portion of the HPRT gene 
was deleted, and RNA splicing was missing in both mutants. A 4-bp deletion at 
the 5' end of exon 4 resulted in formation of three different types of abnormal 
mRNA (Case 4). The other mutant (Case 5) produced abnormal mRNA including 26 bp 
of intron 8 instead of the deleted 58 bp at the 5' end of exon 9, because of a 
74-bp deletion from intron 8 to exon 9.