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.
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.
Authors: Annet M Bosch; Lodewijk Ijlst; Wendy Oostheim; Joyce Mulders; Henk D Bakker; Frits A Wijburg; Ronald J A Wanders; Hans R Waterham Journal: Hum Mutat Date: 2005-05 Impact factor: 4.878
Authors: Ruslan Dorfman; Andrew Sandford; Chelsea Taylor; Baisong Huang; Daisy Frangolias; Yongqian Wang; Richard Sang; Lilian Pereira; Lei Sun; Yves Berthiaume; Lap-Chee Tsui; Peter D Paré; Peter Durie; Mary Corey; Julian Zielenski Journal: J Clin Invest Date: 2008-03 Impact factor: 14.808
Authors: L Varela-Lema; L Paz-Valinas; G Atienza-Merino; R Zubizarreta-Alberdi; R Vizoso Villares; M López-García Journal: J Inherit Metab Dis Date: 2016-04-26 Impact factor: 4.982