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Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity

BACKGROUND: Classic galactosemia (OMIM #230400) is an autosomal recessive metabolic disorder caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT, EC2.7.7.12) protein due to mutations in the GALT gene. The aim of this study was to provide a comprehensive and updated mutation s...

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Autores principales: Choi, Rihwa, Jo, Kyoung Il, Ko, Dae-Hyun, Lee, Dong Hwan, Song, Junghan, Jin, Dong-Kyu, Ki, Chang-Seok, Lee, Soo-Youn, Kim, Jong-Won, Lee, Yong-Wha, Park, Hyung-Doo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236512/
https://www.ncbi.nlm.nih.gov/pubmed/25124065
http://dx.doi.org/10.1186/s12881-014-0094-5
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author Choi, Rihwa
Jo, Kyoung Il
Ko, Dae-Hyun
Lee, Dong Hwan
Song, Junghan
Jin, Dong-Kyu
Ki, Chang-Seok
Lee, Soo-Youn
Kim, Jong-Won
Lee, Yong-Wha
Park, Hyung-Doo
author_facet Choi, Rihwa
Jo, Kyoung Il
Ko, Dae-Hyun
Lee, Dong Hwan
Song, Junghan
Jin, Dong-Kyu
Ki, Chang-Seok
Lee, Soo-Youn
Kim, Jong-Won
Lee, Yong-Wha
Park, Hyung-Doo
author_sort Choi, Rihwa
collection PubMed
description BACKGROUND: Classic galactosemia (OMIM #230400) is an autosomal recessive metabolic disorder caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT, EC2.7.7.12) protein due to mutations in the GALT gene. The aim of this study was to provide a comprehensive and updated mutation spectrum of GALT in a Korean population. METHODS: Thirteen unrelated patients screened positive for galactosemia in a newborn screening program were included in this study. They showed a reduced GALT enzyme activity in red blood cells. Direct sequencing of the GALT gene and in silico analyses were done to evaluate the impact of novel variations upon GALT enzyme activity. We also reviewed previous reports for GALT mutations in Koreans. RESULTS: We identified six novel likely pathogenic variations including three missense (p.Ala101Asp, p.Tyr165His, and p.Pro257Thr), one small deletion/insertion [c.826_827delinsAA (p.Ala276Asn)], one frameshift (p.Asn96Serfs*5), and one splicing (c.378-1G > C) likely pathogenic variations. The most frequent variation was the Duarte variant (c.940A > G, 35.3%), followed by c.507G > C (p.Gln169His, 9.6%), among 34 Korean patients. Other mutations were widely scattered. None of the eight common mutations used for targeted mutation analysis in Western countries including p.Gln188Arg, p.Ser135Leu, p.Lys285Asn, p.Leu195Pro, p.Tyr209Cys, p.Phe171Ser, c.253-2A > G, and a 5 kb deletion, had been found in Koreans until this study. CONCLUSIONS: Considering the mutation spectrum in Koreans, direct sequence analysis of entire GALT exons is recommended for accurate diagnosis. The mutations responsible for GALT deficiency in the Korean population were clearly different from those of other populations.
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spelling pubmed-42365122014-11-19 Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity Choi, Rihwa Jo, Kyoung Il Ko, Dae-Hyun Lee, Dong Hwan Song, Junghan Jin, Dong-Kyu Ki, Chang-Seok Lee, Soo-Youn Kim, Jong-Won Lee, Yong-Wha Park, Hyung-Doo BMC Med Genet Research Article BACKGROUND: Classic galactosemia (OMIM #230400) is an autosomal recessive metabolic disorder caused by a deficiency of the galactose-1-phosphate uridyltransferase (GALT, EC2.7.7.12) protein due to mutations in the GALT gene. The aim of this study was to provide a comprehensive and updated mutation spectrum of GALT in a Korean population. METHODS: Thirteen unrelated patients screened positive for galactosemia in a newborn screening program were included in this study. They showed a reduced GALT enzyme activity in red blood cells. Direct sequencing of the GALT gene and in silico analyses were done to evaluate the impact of novel variations upon GALT enzyme activity. We also reviewed previous reports for GALT mutations in Koreans. RESULTS: We identified six novel likely pathogenic variations including three missense (p.Ala101Asp, p.Tyr165His, and p.Pro257Thr), one small deletion/insertion [c.826_827delinsAA (p.Ala276Asn)], one frameshift (p.Asn96Serfs*5), and one splicing (c.378-1G > C) likely pathogenic variations. The most frequent variation was the Duarte variant (c.940A > G, 35.3%), followed by c.507G > C (p.Gln169His, 9.6%), among 34 Korean patients. Other mutations were widely scattered. None of the eight common mutations used for targeted mutation analysis in Western countries including p.Gln188Arg, p.Ser135Leu, p.Lys285Asn, p.Leu195Pro, p.Tyr209Cys, p.Phe171Ser, c.253-2A > G, and a 5 kb deletion, had been found in Koreans until this study. CONCLUSIONS: Considering the mutation spectrum in Koreans, direct sequence analysis of entire GALT exons is recommended for accurate diagnosis. The mutations responsible for GALT deficiency in the Korean population were clearly different from those of other populations. BioMed Central 2014-08-15 /pmc/articles/PMC4236512/ /pubmed/25124065 http://dx.doi.org/10.1186/s12881-014-0094-5 Text en Copyright © 2014 Choi et al.; licensee BioMed Central Ltd http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Choi, Rihwa
Jo, Kyoung Il
Ko, Dae-Hyun
Lee, Dong Hwan
Song, Junghan
Jin, Dong-Kyu
Ki, Chang-Seok
Lee, Soo-Youn
Kim, Jong-Won
Lee, Yong-Wha
Park, Hyung-Doo
Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity
title Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity
title_full Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity
title_fullStr Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity
title_full_unstemmed Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity
title_short Novel GALT variations and mutation spectrum in the Korean population with decreased galactose-1-phosphate uridyltransferase activity
title_sort novel galt variations and mutation spectrum in the korean population with decreased galactose-1-phosphate uridyltransferase activity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4236512/
https://www.ncbi.nlm.nih.gov/pubmed/25124065
http://dx.doi.org/10.1186/s12881-014-0094-5
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