[Variant phenotype of Lesch-Nyhan syndrome]

Abstract

Background and objective: 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.

Patient and methods: 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.

Results: 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.

Conclusions: 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.