Higher frequency of the galactose-1-phosphate uridyl transferase gene K285N mutation in the Slovenian population

Lukac-Bajalo, Jana; Kuželički, Nataša Karas; Žitnik, Irena Prodan; Mencej, Simona; Battelino, Tadej

doi:10.1016/j.clinbiochem.2006.11.004

Cited by 11 publications

(8 citation statements)

References 10 publications

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“…This mutation is particularly frequent in countries of Central and Eastern Europe, accounting for 26–34% of galactosemic alleles (Greber-Platzer et al 1997; Kozák et al 1999; Lukac-Bajalo et al 2007; Suzuki et al 2001; Zekanowski et al 1999). The Czech, Slovak, Polish, and Austrian galactosemic populations present the highest p.K285N frequencies relatively to other European populations, suggesting a Slavic origin.…”

Section: The Molecular Biology Of Classic Galactosemiamentioning

confidence: 99%

Sweet and sour: an update on classic galactosemia

Coelho

Rubio-Gozalbo

Vicente

et al. 2017

J of Inher Metab Disea

108

125

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Classic galactosemia is a rare inherited disorder of galactose metabolism caused by deficient activity of galactose-1-phosphate uridylyltransferase (GALT), the second enzyme of the Leloir pathway. It presents in the newborn period as a life-threatening disease, whose clinical picture can be resolved by a galactose-restricted diet. The dietary treatment proves, however, insufficient in preventing severe long-term complications, such as cognitive, social and reproductive impairments. Classic galactosemia represents a heavy burden on patients’ and their families’ lives. After its first description in 1908 and despite intense research in the past century, the exact pathogenic mechanisms underlying galactosemia are still not fully understood. Recently, new important insights on molecular and cellular aspects of galactosemia have been gained, and should open new avenues for the development of novel therapeutic strategies. Moreover, an international galactosemia network has been established, which shall act as a platform for expertise and research in galactosemia. Herein are reviewed some of the latest developments in clinical practice and research findings on classic galactosemia, an enigmatic disorder with many unanswered questions warranting dedicated research.

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Section: The Molecular Biology Of Classic Galactosemiamentioning

confidence: 99%

Sweet and sour: an update on classic galactosemia

Coelho

Rubio-Gozalbo

Vicente

et al. 2017

J of Inher Metab Disea

108

125

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“…Homozygous p.Q188R patients have essentially no GALT activity in red blood cells (RBC), displaying a poor outcome (Sommer et al 1995;Tyfield et al 1999). p.K285N is the second most common European mutation, particularly in central and eastern Europe (Lukac-Bajalo et al 2007). p.K285N homozygotes completely lack RBC GALT activity, presenting a severe clinical phenotype (Sommer et al 1995;Tyfield et al 1999).…”

Section: Introductionmentioning

confidence: 99%

A frequent splicing mutation and novel missense mutations color the updated mutational spectrum of classic galactosemia in Portugal

Coelho

Ramos

Gaspar

et al. 2013

J of Inher Metab Disea

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Classic galactosemia is an autosomal recessive disorder caused by deficient galactose-1-phosphate uridylyltransferase (GALT) activity. Patients develop symptoms in the neonatal period, which can be ameliorated by dietary restriction of galactose. Many patients develop long-term complications, with a broad range of clinical symptoms whose pathophysiology is poorly understood. The high allelic heterogeneity of GALT 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-phenotype correlations. Direct sequencing of the GALT 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-up 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-phenotype correlation in classic galactosemia, a monogenic disease whose complex pathogenesis and clinical features emphasize the need to expand the knowledge on this "cloudy" disorder.

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“…The p.Lys285Asn GALT mutation was found to be the second most common mutation in the Greek Cypriot population, occurring with an allele frequency of 30%, similar to that in populations of East and Central Europe where the frequency is 25%–40% (Lukac‐Bajalo et al., ; Tyfield et al., ). The frequency of the p.Lys285Asn mutation is lower in Western European countries, having a frequency of zero in Ireland and Portugal and 3% in the United Kingdom (Coelho et al., ; Murphy et al., ; Tyfield et al., ), showing a general trend to increase in a southeastern direction, but again Greece and Turkey are exceptions having a relatively low frequency of 3.6% and 9%, respectively (Ozgul et al., ; Schulpis et al., ).…”

Section: Discussionmentioning

confidence: 81%

“…The frequency of the p.Lys285Asn mutation is lower in Western European countries, having a frequency of zero in Ireland and Portugal and 3% in the United Kingdom (Coelho et al, 2013;Murphy et al, 1999;Tyfield et al, 1999), showing a general trend to increase in a southeastern direction, but again Greece and Turkey are exceptions having a relatively low frequency of 3.6% and 9%, respectively (Ozgul et al, 2013;Schulpis et al, 2017). It has been suggested that this mutation has a Slavic origin (Kozak et al, 2000;Lukac-Bajalo et al, 2007). Furthermore, the p.Lys285Asn is more geographically restricted compared to p.Gln188Arg because it has appeared after the main population expansions (Flanagan et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Classic galactosaemia in the Greek Cypriot population: An epidemiological and molecular study

Papachristoforou

Petrou

Sawyer

et al. 2019

Annals of Human Genetics

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Classic galactosaemia is an inherited metabolic disorder of galactose metabolism caused by deficiency of the enzyme galactose‐1‐phosphate uridyltransferase (GALT) resulting from mutations in the GALT gene. The objectives of the present study were the determination of the carrier frequency of classic galactosaemia in the Greek Cypriot population and the molecular characterization of the disease alleles. We performed an epidemiological study involving 528 Greek Cypriots originating from all parts of Cyprus. Carriers were identified by measuring GALT activity in red blood cells and were subsequently subjected to mutation analysis. A total of five mutations were identified in patients and carriers of classic galactosaemia: a large deletion of 8.5 kb previously reported by us (55% of alleles), the known mutations p.Lys285Asn (30%), p.Pro185Ser (5%), and c.820+13A>G (5%), and a novel mutation c.378‐12G>A (5%). Interestingly, the most common mutation in European populations, p.Gln188Arg, was not identified in this Cypriot cohort. The carrier frequency for classic galactosaemia among Greek Cypriots was estimated to be 1:88, predicting a homozygote incidence of 1:31,000 births. The Duarte 1 and Duarte 2 variants were found to be present at a frequency of 5.5% and 2.5%, respectively.

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Higher frequency of the galactose-1-phosphate uridyl transferase gene K285N mutation in the Slovenian population

Cited by 11 publications

References 10 publications

Sweet and sour: an update on classic galactosemia

Sweet and sour: an update on classic galactosemia

A frequent splicing mutation and novel missense mutations color the updated mutational spectrum of classic galactosemia in Portugal

Classic galactosaemia in the Greek Cypriot population: An epidemiological and molecular study

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