caa a22 4500 475786939 CHVBK 20180406123701.0 cr unu---uuuuu 170329e20001201xx s 000 0 eng 10.1007/PL00014404 doi (NATIONALLICENCE)springer-10.1007/PL00014404 Tyfield Linda A. Molecular Genetics Unit, The Lewis Laboratories, Southmead Hospital, Bristol BS10 5NB, UK e-mail: linda.tyfield@bris.ac.uk Tel.: +44-117-9595565; Fax: +44-117-9591792, GB aut Galactosaemia and allelic variation at the galactose-1-phosphate uridyltransferase gene: a complex relationship between genotype and phenotype [Elektronische Daten] [Linda A. Tyfield] More than 160 different base changes have been described at the galactose-1-phosphate uridyltransferase gene and most of these are associated with a disease phenotype. Q188R is the most common mutation in north European populations and those predominantly of European descent. K285N is much rarer but in some countries of east/central Europe it is the second most common mutation. In some populations of northern Europe these two mutations can be found on 70%-80% of mutant chromosomes. Both mutations appear to be associated with a complete loss in enzyme activity and thus, a more severe biochemical phenotype. A single amino acid substitution, N314D, is found on both Duarte 1 and Duarte 2 alleles. Additional base changes that are different on each distinguish D1 from D2 alleles. Whether the differences in galactose-1-phosphate uridyltransferase enzyme activities are associated with the additional molecular changes that distinguish D1 and D2 alleles remains unclear. S135L is found almost exclusively in galactosaemic individuals of African origin. Despite early diagnosis and treatment and adherence to a lactose free diet neurological complications, poor growth and reduced fertility are frequently observed in affected individuals. Conclusion Allelic variation at the galactose-1-phosphate uridyltransferase gene undoubtedly plays a role in defining the biochemical and clinical phenotype. However, clinical galactosaemia is a complex trait in which multiple developmental and metabolic pathways are involved. Ultimately the phenotype is beyond the control of the single gene itself. Springer-Verlag Berlin Heidelberg, 2000 Key words Allelic heterogeneity nationallicence Galactosaemia nationallicence Galactose-1-phosphate uridyltransferase nationallicence Mutation nationallicence https://doi.org/10.1007/PL00014404 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00014404 text/html Onlinezugriff via DOI NATIONALLICENCE 100 1- Tyfield Linda A. Molecular Genetics Unit, The Lewis Laboratories, Southmead Hospital, Bristol BS10 5NB, UK e-mail: linda.tyfield@bris.ac.uk Tel.: +44-117-9595565; Fax: +44-117-9591792, GB aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer