title: Analysis of the HPRT1 gene in 35 Italian Lesch-Nyhan families: 45 patients and 77 potential female carriers.
abstract: BACKGROUND
  Lesch-Nyhan (LND) disease is an inborn error of purine metabolism which results from deficiency of the activity of hypoxanthine-guanine phosphoribosyltransferase (HPRT). In the classical form of the disease the activity of the enzyme is completely deficient and the patient has cognitive impairment, spasticity, dystonia and self-injurious behaviour, as well as elevated concentrations of uric acid in blood and urine that leads to consequences such as nephropathy, urinary tract calculi and tophaceous gout. There are disease variants without self-injurious behaviour. In these cases neurological manifestations may vary widely. The HPRT1 gene is located on the X chromosome in position Xq26-27.2, and mutations have been found in quite a large number of patients.
  
  
  OBJECTIVE
  Documenting our experience with the diagnosis of LND in 45 Italian patients from 35 nonrelated families and 77 females at risk of being carriers of the condition.
  
  
  METHODS
  Internal review.
  
  
  METHODS
  An institute devoted to the investigation and care of patients with rare diseases.
  
  
  RESULTS
  In 94% of the LND families gDNA sequencing of the patients was informative while in 6% a cDNA study was required. For the carrier females gDNA sequencing was informative in 71% of the families, 23% required qPCR studies and 6% required segregation studies combined with enzymatic activity testing. Classical cDNA studies proved to be unreliable in carrier females as there is a significant risk of failure to detect the mutated allele. Four novel HPRT1 mutations were found: c.145C>T (p.Leu49Phe), c.112C>T (p.Pro38Ser), c.89_96dup8 (p.Glu33Argfs) and c.506dupC (p.Arg170Thrfs).
  
  
  CONCLUSIONS
  In the diagnosis of LND it is very important to consider all the possible alterations of the HPRT1 gene when searching for mutations especially if no affected male is available. Biochemical assessment of the enzymatic activity of HPRT in an affected male is the ideal starting point for molecular analysis of the gene.
authors.affiliation: Mauro Baschirotto Institute for Rare Diseases, B.I.R.D. Foundation, 36023 Costozza di Longare, Vicenza, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: de Gemmis
authors.forename: Laura
authors.initials: L
authors.lastname: Anesi
authors.forename: Elisa
authors.initials: E
authors.lastname: Lorenzetto
authors.forename: Ilenia
authors.initials: I
authors.lastname: Gioachini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Fortunati
authors.forename: Gessica
authors.initials: G
authors.lastname: Zandonà
authors.forename: Erika
authors.initials: E
authors.lastname: Fanin
authors.forename: Lynette
authors.initials: L
authors.lastname: Fairbanks
authors.forename: Gilberto
authors.initials: G
authors.lastname: Andrighetto
authors.forename: Pietro
authors.initials: P
authors.lastname: Parmigiani
authors.forename: Diego
authors.initials: D
authors.lastname: Dolcetta
authors.forename: William L
authors.initials: WL
authors.lastname: Nyhan
authors.forename: Uros
authors.initials: U
authors.lastname: Hladnik
mesh_terms: D005192:Family Health; D005260:Female; D006579:Heterozygote; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics*; D007558:Italy; D007926:Lesch-Nyhan Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation
chemical_list: D007041:Hypoxanthine Phosphoribosyltransferase