More than 100 mutations of the HPRT gene have been described related to Lesch-Nyhan syndrome in complete lack of enzyme activity, or KelleySeegmiller syndrome in partial enzyme deficiency. We examined (modified according to genomic DNA from an 11-year-old boy, S.Z., with -1% HPRT activity, who had presented with acute renal failure in the early postnatal period (Wingen et al., 1987) without neurological symptoms.
In the initiation codon (ATG), a T + C transition was identified that leads to substitution of Met 1 by Thr. This mutation was shown also in the mother and maternal grandfather, who were heterozygeous and hemizygeous, respectively. No other alteration in comparison to the wild-type sequence was observed.
Only two mutations affecting the initiation codon of the HPRT gene have been reported: ATG + ATA in a Lesch-Nyhan patient (Tar16 et al., 1991) and a 13 base deletion, which creates a functional GTG initiation codon in a patient with partial HPRT deficiency .
In alternative initiation codons such as CTG, GTG, and ACG, a translation of 10-30%, in ATA and ATT of -5% efficiency was observed in mammalian cells (Mehdi et al., 1990). The ACG codon detected in S.Z. may serve as an alternative initiation codon comparable to the GTG start codon mutation described before.
ACKNOWLEDGMENT
Stiftung".