{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:42:07Z","timestamp":1762004527831},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,6,8]],"date-time":"2013-06-08T00:00:00Z","timestamp":1370649600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Classic galactosemia is an autosomal recessive disorder caused by deficient galactose\u20101\u2010phosphate uridylyltransferase (GALT) activity. Patients develop symptoms in the neonatal period, which can be ameliorated by dietary restriction of galactose. Many patients develop long\u2010term complications, with a broad range of clinical symptoms whose pathophysiology is poorly understood. The high allelic heterogeneity of <jats:italic>GALT<\/jats:italic> gene that characterizes this disorder is thought to play a determinant role in biochemical and clinical phenotypes. We aimed to characterize the mutational spectrum of GALT deficiency in Portugal and to assess potential genotype\u2010phenotype correlations. Direct sequencing of the <jats:italic>GALT<\/jats:italic> gene and in silico analyses were employed to evaluate the impact of uncharacterized mutations upon GALT functionality. Molecular characterization of 42 galactosemic Portuguese patients revealed a mutational spectrum comprising 14 nucleotide substitutions: ten missense, two nonsense and two putative splicing mutations. Sixteen different genotypic combinations were detected, half of the patients being p.Q188R homozygotes. Notably, the second most frequent variation is a splicing mutation. In silico predictions complemented by a close\u2010up on the mutations in the protein structure suggest that uncharacterized missense mutations have cumulative point effects on protein stability, oligomeric state, or substrate binding. One splicing mutation is predicted to cause an alternative splicing event. This study reinforces the difficulty in establishing a genotype\u2010phenotype correlation in classic galactosemia, a monogenic disease whose complex pathogenesis and clinical features emphasize the need to expand the knowledge on this \u201ccloudy\u201d disorder.<\/jats:p>","DOI":"10.1007\/s10545-013-9623-1","type":"journal-article","created":{"date-parts":[[2013,6,7]],"date-time":"2013-06-07T07:15:02Z","timestamp":1370589302000},"page":"43-52","source":"Crossref","is-referenced-by-count":12,"title":["A frequent splicing mutation and novel missense mutations color the updated mutational spectrum of classic galactosemia in Portugal"],"prefix":"10.1002","volume":"37","author":[{"given":"Ana I.","family":"Coelho","sequence":"first","affiliation":[{"name":"Metabolism &amp; Genetics Group, Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy University of Lisbon Av. Prof. Gama Pinto Lisbon 1643\u2010009 Portugal"},{"name":"Department of Biochemistry and Human Biology, Faculty of Pharmacy University of Lisbon Lisbon Portugal"}]},{"given":"Ruben","family":"Ramos","sequence":"additional","affiliation":[{"name":"Metabolism &amp; Genetics Group, Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy University of Lisbon Av. Prof. Gama Pinto Lisbon 1643\u2010009 Portugal"},{"name":"Department of Biochemistry and Human Biology, Faculty of Pharmacy University of Lisbon Lisbon Portugal"}]},{"given":"Ana","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hospital Santa Maria Lisbon Portugal"}]},{"given":"Cl\u00e1udia","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hospital Santa Maria Lisbon Portugal"}]},{"given":"Anabela","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Medicine Hospital Santa Maria Lisbon Portugal"}]},{"given":"Lu\u00edsa","family":"Diogo","sequence":"additional","affiliation":[{"name":"Metabolic Clinics, Pediatric Hospital CHUC Coimbra Portugal"}]},{"given":"Paula","family":"Garcia","sequence":"additional","affiliation":[{"name":"Metabolic Clinics, Pediatric Hospital CHUC Coimbra Portugal"}]},{"given":"Sandra","family":"Paiva","sequence":"additional","affiliation":[{"name":"Metabolic Clinics, Pediatric Hospital CHUC Coimbra Portugal"}]},{"given":"Esmeralda","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hospital Santo Ant\u00f3nio Porto Portugal"}]},{"given":"Elisa Le\u00e3o","family":"Teles","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Unit, Integrated Pediatric Hospital Hospital S\u00e3o Jo\u00e3o Porto Portugal"}]},{"given":"Esmeralda","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Unit, Integrated Pediatric Hospital Hospital S\u00e3o Jo\u00e3o Porto Portugal"}]},{"given":"M. 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