title: High incidence and allelic homogeneity of Wilson disease in 2 isolated populations: a prerequisite for efficient disease prevention programs.
abstract: OBJECTIVE
  Herein we report the results of mutation-based screening for Wilson disease (WD) in 2 isolated populations of Sardinia and the Greek island of Kalymnos.
  
  
  METHODS
  Mutation analysis was performed in 110 and 9 WD families originating respectively from Sardinia and Kalymons using single-strand conformation polymorphism and sequencing methods. In Sardinia, a limited screening was performed for -441/-427del in 5290 newborns, whereas in Kalymnos 397 newborns underwent mutation screening for H1069Q and R969Q using appropriate methods.
  
  
  RESULTS
  In Sardinia, mutation analysis showed the presence of 6 mutations accounting for 85% of chromosomes, 1 of which (-441/-427del) is present in 61.7% of alleles. The screening for -441/-427del in 5290 newborns revealed the presence of 122 heterozygotes, which is equal to an allelic frequency of 1.15%. Assuming the same distribution of WD mutations in the general Sardinian population, we also inferred an allelic frequency of 0.77% for mutations other than -441/-427del, which accounts for an overall frequency of any WD mutation of 1.92%. Assuming Hardy-Weinberg equilibrium, these data could be translated into a WD incidence of 1 in 2707 live births. In Kalymnos, mutation analysis in 9 WD families revealed the presence of only 2 mutations. The screening of 397 newborns revealed the presence of 18 heterozygotes for H1069Q, 9 for R969Q, and 1 compound heterozygote for these mutations, which is equal to an allele frequency of 3.7%. Assuming Hardy-Weinberg equilibrium, the expected carrier rate is 7%.
  
  
  CONCLUSIONS
  These data indicate the need for health education for WD prevention in these isolated populations.
authors: Dipartimento di Scienze Biomediche e Biotecnologie, USC, Italy.
authors: Antonietta
authors: A
authors: Zappu
authors: Olympia
authors: O
authors: Magli
authors: Maria Barbara
authors: MB
authors: Lepori
authors: Valentina
authors: V
authors: Dessì
authors: Stefania
authors: S
authors: Diana
authors: Simona
authors: S
authors: Incollu
authors: Emmanuel
authors: E
authors: Kanavakis
authors: Polyxeni
authors: P
authors: Nicolaidou
authors: Nina
authors: N
authors: Manolaki
authors: Andreas
authors: A
authors: Fretzayas
authors: Stefano
authors: S
authors: De Virgiliis
authors: Antonio
authors: A
authors: Cao
authors: Georgios
authors: G
authors: Loudianos
mesh_terms: D002570:Ceruloplasmin / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005828:Genetics, Population; D005838:Genotype; D006115:Greece / Q000453:epidemiology; D006527:Hepatolenticular Degeneration / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007558:Italy / Q000453:epidemiology; D008297:Male; D009154:Mutation; D015997:Neonatal Screening; D018807:Polymorphism, Single-Stranded Conformational; D012307:Risk Factors; D017384:Sequence Deletion
chemical_list: D003300:Copper; D002570:Ceruloplasmin