Zusammenfassung
HINTERGRUND: Die klassische Galaktosämie ist eine autosomal rezessiv vererbte Erkrankung, die durch eine gestörte Aktivität der Galactose-1-phosphat-Uridyltransferase verursacht wird und die im Rahmen eines Neugeborenen-Screenings erkannt werden kann. In Ungarn wurde das Neugeborenen-Screening 1976 eingeführt, es wird in 2 Zentren durchgeführt. Ziel der vorliegenden Studie war die molekulare Charakteriserung des Genotyps und die Analyse der Genotyp-Phänotyp-Korrelation bei Patienten mit der klassischen bzw. mit der Variante der Galaktosämie. PATIENTEN UND METHODEN: DNS Proben von 40 Patienten wurden mittels Polymerase-Kettenreaktion, gefolgt von direkter Sequenzierung untersucht. Die klinischen Daten wurden im Hinblick auf die gefundenen Genotypen analysiert. ERGEBNISSE: 16 verschiedene Sequenzvariationen wurden identifiziert, wobei auch 2 neue Missense-Mutationen (p.S297P, p.E146D) erfasst wurden. Die zwei am häufigsten gefundenen Mutationen waren p.Q188R und p.K285N mit einer Allel-Häufigkeit von 45% bzw. 31,2%. SCHLUSSFOLGERUNGEN: Die klinisch am schwersten verlaufenden Phänotypen waren in unserer Bevölkerung mit p.Q188R, p.K285N, p.X380R, p.S297P, p.M142K, p.R.204X, p.Q169K, und p.R407P Mutationen assoziiert. Die Manifestationen hängen aber von anderen genetischen und auch Umweltfaktoren ab.
Summary
BACKGROUND: Classic galactosemia is an autosomal recessively inherited disorder caused by deficient activity of the enzyme galactose-1-phosphate uridyltransferase. The disorder can be detected by newborn screening and in Hungary the national screening program was launched in 1976 with two screening centers. The aim of this study was the molecular characterization of the genotypes and analysis of genotype-phenotype correlation among patients with classic or variant galactosemia. PATIENTS AND METHODS: DNA samples from 40 patients were analyzed by polymerase chain reaction followed by direct sequencing. RESULTS: 16 different sequence variations were identified, including two novel missense mutations (p.S297P, p.E146D). The two most common mutations were p. Q188R and p.K285N with allele frequencies of 45% and 31.2%, respectively. Clinical data were evaluated with respect to the genotypes found. CONCLUSIONS: The most serious clinical phenotypes in our population were associated with mutations p. Q188R, p.K285N, p.X380R, p.S297P, p.M142K, p.R.204X, p.Q169K and p.R407P, but manifestations depend on other genetic and environmental factors.
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Milánkovics, I., Schuler, Á., Kámory, E. et al. Molecular and clinical analysis of patients with classic and Duarte galactosemia in western Hungary. Wien Klin Wochenschr 122, 95–102 (2010). https://doi.org/10.1007/s00508-010-1311-7
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DOI: https://doi.org/10.1007/s00508-010-1311-7