title: HPRTYale proposed as a pathogenic variant for Lesch-Nyhan syndrome: a case report.
abstract: Lesch-Nyhan syndrome (LNS) is an X-linked recessive disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT), an enzyme encoded by the HPRT1 gene. The classic disease phenotype described by Lesch and Nyhan in 1964 includes hyperuricemia, mental retardation, severe motor deficiency, and recurring self-mutilation. 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. The same patient was studied by Wilson et al. in 1986, who found no detectable HPRT enzymatic activity, even though normal HPRT mRNA and protein levels were observed. Disease severity is closely related to residual enzymatic activity, which fits the phenotype presented for this previously reported case, as well as for the patients we report on herein. As it has been reported in only one patient, this mutation is still considered a variant of unknown significance. The HPRTYale mutation is a G>C transversion that leads to a different amino acid with different biochemical properties at position 71, potentially causing the major lack of function. To evaluate the impact of this variant, we used the PolyPhen-2 software, which classified it as possibly damaging. Furthermore, the frequency of this mutant allele is likely extremely rare, since it has only been reported on twice, and a population frequency is not yet available. In conclusion, we propose that the HPRTYale variant is pathogenic, and should be included on lab reports hereafter.
authors.affiliation: Núcleo de Genética Humana e Molecular, Departamento de Ciências Biológicas, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.|Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: E
authors.initials: E
authors.lastname: Stur
authors.affiliation: Núcleo de Genética Humana e Molecular, Departamento de Ciências Biológicas, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.|Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: R S
authors.initials: RS
authors.lastname: Reis
authors.affiliation: Núcleo de Genética Humana e Molecular, Departamento de Ciências Biológicas, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.|Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: L P
authors.initials: LP
authors.lastname: Agostini
authors.affiliation: Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.|Departamento de Biologia, Universidade Federal do Espírito Santo, Alegre, ES, Brasil.
authors.forename: A M A
authors.initials: AM
authors.lastname: Silva-Conforti
authors.affiliation: Núcleo de Genética Humana e Molecular, Departamento de Ciências Biológicas, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.|Programa de Pós-Graduação em Biotecnologia, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.
authors.forename: I D
authors.initials: ID
authors.lastname: Louro
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D006579:Heterozygote; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007926:Lesch-Nyhan Syndrome / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase