Here, we report the case of a family with 4 affected males and several female obligate carriers.In 1989, Fujimori et al. reported on a patient diagnosed with LNS who had an HPRT variant thereafter codenamed HPRTYale.
Lesch-Nyhan disease (LND) is a rare X-linked recessive genetic disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme.
In the current review, we highlight the role of miRNAs in Lesch-Nyhan disease (LND), a rare neurogenetic syndrome caused by mutations in the purine metabolic gene encoding the hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme.
Lesch-Nyhan disease (LND) is an X-linked genetic disorder caused by mutations of the hypoxanthine guanine phosphoribosyltransferase (HPRT) purine biosynthesis gene and characterized by aberrant purine metabolism, deficient basal ganglia dopamine levels, dystonia, and severe neurobehavioral manifestations, including compulsive self-injurious behavior.
A healthy female with a brother suffering from Lesch-Nyhan syndrome was assigned a carrier status on the basis of haplotype analysis employing flanking and intragenic polymorphic markers of the HPRT gene.
Although these 'evolutionary conserved' amino acids account for only 32% of the amino acids in the human hprt protein, they are involved in 76% of the missense mutations at the hprt locus in human T-lymphocytes, 67% in Lesch-Nyhan patients (with severe hprt-deficiency), but only 43% in gout patients (with partial hprt deficiency).
Molecular description of three macro-deletions and an Alu-Alu recombination-mediated duplication in the HPRT gene in four patients with Lesch-Nyhan disease.
Sequencing analysis of the amplified DNA from three different patients with HPRT deficiency implied three unique molecular abnormalities: 1) one single-base substitution at codon 54 (from ATG to CTG) resulting in the replacement of methionine with leucine in an LN patient, 2) two single-base substitutions at codon 179 (from GTT to GGT) and at codon 180 (from GGA to AGA) resulting in the replacement of valine with glycine and glycine with arginine in a gouty patient, and 3) 51 nucleotide deletion between nucleotides 747 and 797 resulting in the formation of shorter sized HPRT mRNA and putative two amino-acid deleted HPRT protein in another gouty patient.
Inherited mutations in the human HPRT1 gene result in three different phenotypes: Lesch-Nyhan syndrome (LNS or LND), LND variants, and HPRT-related hyperuricemia (HRH).
In contrast with the most severe phenotype of classical Lesch-Nyhan disease (LND), the least severe phenotype is characterized by hyperuricemia without any neurological or behavioral abnormality, and designated HPRT-related hyperuricemia (HRH).
Mutations in the X chromosome hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene are responsible for Lesch-Nyhan syndrome and related diseases in humans.
Up to 25-30% of HPRT deficient patients, indicated as neurological variants or HPRT-related hyperuricemia with neurological dysfunction (HRND), may develop neurological manifestation, from mild to severe; the most serious ones manifesting in the devastating Lesch-Nyhan syndrome, characterized by choreoathetosis or self-mutilation.