TY - JOUR
TI - High incidence and allelic homogeneity of wilson disease in 2 isolated populations: A prerequisite for efficient disease prevention programs
AU - Antonietta, Z.
AU - Olympia, M.
AU - Lepori, M.B.
AU - Valentina, D.
AU - Stefania, D.
AU - Simona, I.
AU - Emmanuel, K.
AU - Polyxeni, N.
AU - Nina, M.
AU - Andreas, F.
AU - Stefano, D.V.
AU - Antonio, C.
AU - Georgios, L.
JO - Journal of Pediatric Gastroenterology and Nutrition,
PY - 2008
VL - 47
TODO - 3
SP - 334-338
PB - 
SN - 0277-2116
TODO - 10.1097/MPG.0b013e31817094f6
TODO - allele;  article;  cell free system;  chromosome mutation;  controlled study;  drug screening;  gene frequency;  Greece;  health education;  heterozygosity;  human;  human cell;  human tissue;  incidence;  kidney homogenate;  liver homogenate;  mutation;  mutation rate;  priority journal;  screening test;  Wilson disease;  female;  gene deletion;  genetic predisposition;  genetic screening;  genetics;  genotype;  Greece;  heterozygote detection;  Italy;  male;  metabolism;  mutation;  newborn;  newborn screening;  nucleotide sequence;  population genetics;  risk factor;  single strand conformation polymorphism;  Wilson disease, ceruloplasmin;  copper, Ceruloplasmin;  Copper;  DNA Mutational Analysis;  Female;  Gene Frequency;  Genetic Predisposition to Disease;  Genetic Screening;  Genetics, Population;  Genotype;  Greece;  Hepatolenticular Degeneration;  Heterozygote Detection;  Humans;  Incidence;  Infant, Newborn;  Italy;  Male;  Mutation;  Neonatal Screening;  Polymorphism, Single-Stranded Conformational;  Risk Factors;  Sequence Deletion
TODO - Objectives: 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. Patients and 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. © 2008 by Lippincott Williams & Wilkins.
ER -