High incidence and allelic homogeneity of Wilson disease in 2 isolated populations: a prerequisite for efficient disease prevention programs.
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.
Zappu
Antonietta
A
Dipartimento di Scienze Biomediche e Biotecnologie, USC, Italy.
Magli
Olympia
O
Lepori
Maria Barbara
MB
Dessì
Valentina
V
Diana
Stefania
S
Incollu
Simona
S
Kanavakis
Emmanuel
E
Nicolaidou
Polyxeni
P
Manolaki
Nina
N
Fretzayas
Andreas
A
De Virgiliis
Stefano
S
Cao
Antonio
A
Loudianos
Georgios
G
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
D003300:Copper; D002570:Ceruloplasmin