title: Genotype-phenotype correlation in Italian children with Wilson's disease.
abstract: OBJECTIVE
  Wilson's disease phenotype is very variable for clinical and laboratory features. Our aim was to assess the role of the type of ATP7B disease causing mutations on Wilson's disease phenotype.
  
  
  METHODS
  We retrospectively evaluated the data of children with Wilson's disease from eight pediatric departments.
  
  
  RESULTS
  Fifty-eight patients (34 male, median age at diagnosis 7.4 years) from 47 unrelated families were studied, carrying 34 different mutations. The most common mutations were the missense p.H1069Q and p.M769V, the nonsense p.R1319X, the frameshift c.2299delC, c.2298_2299insC and c.2530delA, and the splice site mutation c.2447+5G>A. Serum ceruloplasmin and copper were lower among the patients' homozygotes for nonsense and frameshift mutations than in patients with missense mutations. A normalization of serum alanine aminotransferase after therapy was not achieved in 23.6% of patients with missense mutations versus 45.5% of patients with nonsense/frameshift mutations. A direct linear correlation was found between age at diagnosis and urinary copper excretion at diagnosis.
  
  
  CONCLUSIONS
  The type of mutation explains at least a part of Wilson's disease phenotype, and mutation analysis should be considered as an integrative tool for such a challenging diagnosis. Urinary copper excretion appears to be correlated to the age at diagnosis rather than genotype.
authors.affiliation: Department of Pediatrics, University of Naples Federico II, Naples, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Nicastro
authors.forename: Georgios
authors.initials: G
authors.lastname: Loudianos
authors.forename: Lucia
authors.initials: L
authors.lastname: Zancan
authors.forename: Lorenzo
authors.initials: L
authors.lastname: D'Antiga
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maggiore
authors.forename: Matilde
authors.initials: M
authors.lastname: Marcellini
authors.forename: Cristiana
authors.initials: C
authors.lastname: Barbera
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Marazzi
authors.forename: Ruggiero
authors.initials: R
authors.lastname: Francavilla
authors.forename: Maria
authors.initials: M
authors.lastname: Pastore
authors.forename: Pietro
authors.initials: P
authors.lastname: Vajro
authors.forename: Mariangela
authors.initials: M
authors.lastname: D'Ambrosi
authors.forename: Angela
authors.initials: A
authors.lastname: Vegnente
authors.forename: Giusy
authors.initials: G
authors.lastname: Ranucci
authors.forename: Raffaele
authors.initials: R
authors.lastname: Iorio
mesh_terms: D019943:Amino Acid Substitution; D002570:Ceruloplasmin / Q000235:genetics; D002648:Child; D018389:Codon, Nonsense; D003300:Copper / Q000097:blood / Q000652:urine; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D006527:Hepatolenticular Degeneration / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007558:Italy; D008111:Liver Function Tests; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D012189:Retrospective Studies; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D003300:Copper; D004247:DNA; D002570:Ceruloplasmin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human