[A Japanese family with Lesch-Nyhan syndrome resulting from a new point mutation in hypoxanthine-guanine phosphoribosyltransferase gene].

Lesch-Nyhan syndrome is associated with complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT), characterized by hyperuricemia and severe neurological signs. The HPRT gene has been mapped to the q26 region on the long arm of the X-chromosome. We are taking care of a family of Lesch-Nyhan syndrome. A 14-year-old male was noted the growth disturbance at the age of 7 months and self-mutilation behavior characterized by compulsive biting of his lip and fingers at the age of 18 months. In 1987, at the age of 4, he was diagnosed as Lesch-Nyhan syndrome from neurologic signs and hyperuricemia (9.8 mg/dl). Neurological examination revealed mild mental and growth retardation, spasticity and hyperreflexia of lower extremities, choreoathetoid movements of extremities, and compulsive self-mutilation. The HPRT activity in erythrocytes of this patient was 0.02 nmol/min/mg hemoglobin (control value 1.76 +/- 0.06), and adenine phosphoribosyltransferase (APRT) activity was 1.08 nmol/min/mg hemoglobin (control value 0.43 +/- 0.06). Using polymerase chain reaction (PCR) method coupled with direct sequencing, we analyzed the nucleotide sequences of each exon from the genomic DNA as well as the entire HPRT coding region of the cDNA by RT-PCR method. In the HPRT gene from the patient, a guanine to adenine substitution at base position 209 in exon 3 was identified, which resulted in a single amino acid substitution of glycine with glutamic acid at codon 70. The family studies indicated that his mother, sister and grandmother were heterozygotes. PCR-restriction fragment length polymorphism (RFLP) utilizing Mnl I site which created by the mutation, was useful for detection of the mutant gene. We have identified a new missense mutation of the HPRT gene in a Japanese patient. This mutation was reported at the same codon as foreign mutants and mighty be indicative of a location of mutation activity in the HPRT gene.