[Variant phenotype of Lesch-Nyhan syndrome]

Lesch-Nyhan syndrome (LNS) and LNS variants are due to mutations in the HPRT1 gene causing HPRT enzymatic activity deficiency. We report a patient presenting a variant phenotype and a major genetic defect. The mutation has been previously reported as always associated with complete Lesch-Nyhan phenotype.

We analyzed the presence of complete HPRT mRNA in this patient, in two patients with the complete Lesch Nyhan syndrome phenotype, and in control subjects.

We found a minor amount of normal HPRT mRNA in the present patient but also in the two patients with splice mutation and the complete Lesch Nyhan syndrome phenotype.

To our knowledge, this patient is the first report of a major genetic defect, with no detectable enzymatic activity, and a partial HPRT deficiency phenotype. Our results question the hypothesis of a normally spliced HPRT cDNA as the sole cause of the patient partial phenotype.