BACKGROUND: The Lesch-Nyhan syndrome is an X-linked recessive inherited disease 
caused by a complete deficiency of hypoxanthine guanine 
phosphoribosyl-transferase (HPRT) activity. Many different mutations throughout 
the HPRT coding region of Lesch-Nyhan patients have been described, including 
single base substitutions, partial or entire gene deletions, gene insertions or 
endoduplication of exons. However, study of gene mutation in Chinese patients 
has rarely been reported in Taiwan.
METHODS: Polymerase chain reaction (PCR) and nucleotide sequence analysis were 
used to identify the location and the nature of the mutation at the HPRT locus 
in two brothers affected with Lesch-Nyhan syndrome. The HPRT cDNA, amplified 
from total RNA of patient's peripheral blood by reverse transcription-polymerase 
chain reaction, was cloned into a pGEM-3Zf(-) vector and then sequenced. Family 
study involved initial screening using single-strand conformation polymorphism, 
and further confirmation by direct sequencing of the exon encompassing the 
mutation.
RESULTS: The mutation identified in these two affected siblings was a single 
nucleotide substitution, from cytosine to guanine, in exon 3 of the HPRT coding 
region. This transversion putatively caused a single amino acid substitution 
from phenylalanine to leucine at codon 74 in the translated protein. This base 
change was further confirmed by direct sequencing of both the HPRT cDNA fragment 
and the exon 3 of HPRT gene amplified from genomic DNA. The family study 
revealed that the patient's mother was a heterozygous carrier, and the mutation 
seemed to have occurred de novo in a germinal cell from one of the maternal 
grandparents.
CONCLUSIONS: This is the first family study on Chinese patients with Lesch-Nyhan 
syndrome identified by molecular analysis in Taiwan. The mutation described 
herein is a novel substitution which occurs in a suggested "hotspot" of mutation 
(exon 3) of the HPRT gene. The application of molecular analysis of HPRT-gene 
allows not only DNA diagnosis by directly detecting the mutant alleles, but also 
prenatal diagnosis and carrier identification within individual families 
affected by Lesch-Nyhan syndrome.