Τίτλος:
High incidence and allelic homogeneity of wilson disease in 2 isolated populations: A prerequisite for efficient disease prevention programs
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Antonietta, Z.
Olympia, M.
Lepori, M.B.
Valentina, D.
Stefania, D.
Simona, I.
Emmanuel, K.
Polyxeni, N.
Nina, M.
Andreas, F.
Stefano, D.V.
Antonio, C.
Georgios, L.
Περιοδικό:
Journal of Pediatric Gastroenterology and Nutrition,
Λέξεις-κλειδιά:
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
DOI:
10.1097/MPG.0b013e31817094f6
