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Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience

The lysosomal storage disorder Fabry disease is caused by deficient or absent activity of the GLA gene enzyme α-galactosidase A. In the present study we present the molecular and biochemical data of the Danish Fabry cohort and report 20 years’ (2001–2020) experience in cascade genetic screening at t...

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Autores principales: Effraimidis, Grigoris, Rasmussen, Åse Krogh, Dunoe, Morten, Hasholt, Lis F., Wibrand, Flemming, Sorensen, Soren S., Lund, Allan M., Kober, Lars, Bundgaard, Henning, Yazdanfard, Puriya D. W., Oturai, Peter, Larsen, Vibeke A., de Abreu, Vitor Hugo Fraga, Enevoldsen, Lotte Hahn, Kristensen, Tatiana, Svenstrup, Kirsten, Bille, Margrethe Bastholm, Arif, Farah, Mogensen, Mette, Klokker, Mads, Backer, Vibeke, Kistorp, Caroline, Feldt-Rasmussen, Ulla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668118/
https://www.ncbi.nlm.nih.gov/pubmed/36383556
http://dx.doi.org/10.1371/journal.pone.0277767
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author Effraimidis, Grigoris
Rasmussen, Åse Krogh
Dunoe, Morten
Hasholt, Lis F.
Wibrand, Flemming
Sorensen, Soren S.
Lund, Allan M.
Kober, Lars
Bundgaard, Henning
Yazdanfard, Puriya D. W.
Oturai, Peter
Larsen, Vibeke A.
de Abreu, Vitor Hugo Fraga
Enevoldsen, Lotte Hahn
Kristensen, Tatiana
Svenstrup, Kirsten
Bille, Margrethe Bastholm
Arif, Farah
Mogensen, Mette
Klokker, Mads
Backer, Vibeke
Kistorp, Caroline
Feldt-Rasmussen, Ulla
author_facet Effraimidis, Grigoris
Rasmussen, Åse Krogh
Dunoe, Morten
Hasholt, Lis F.
Wibrand, Flemming
Sorensen, Soren S.
Lund, Allan M.
Kober, Lars
Bundgaard, Henning
Yazdanfard, Puriya D. W.
Oturai, Peter
Larsen, Vibeke A.
de Abreu, Vitor Hugo Fraga
Enevoldsen, Lotte Hahn
Kristensen, Tatiana
Svenstrup, Kirsten
Bille, Margrethe Bastholm
Arif, Farah
Mogensen, Mette
Klokker, Mads
Backer, Vibeke
Kistorp, Caroline
Feldt-Rasmussen, Ulla
author_sort Effraimidis, Grigoris
collection PubMed
description The lysosomal storage disorder Fabry disease is caused by deficient or absent activity of the GLA gene enzyme α-galactosidase A. In the present study we present the molecular and biochemical data of the Danish Fabry cohort and report 20 years’ (2001–2020) experience in cascade genetic screening at the Danish National Fabry Disease Center. The Danish Fabry cohort consisted of 26 families, 18 index patients (9 males and 9 females, no available data for 8 index-patients) and 97 family members with a pathogenic GLA variant identified by cascade genetic testing (30 males and 67 females). Fourteen patients (5 males and 9 females; mean age of death 47.0 and 64.8 years respectively) died during follow-up. The completeness of the Fabry patient identification in the country has resulted in a cohort of balanced genotypes according to gender (twice number of females compared to males), indicating that the cohort was not biased by referral, and further resulted in earlier diagnosis of the disease by a lower age at diagnosis in family members compared to index-patients (mean age at diagnosis: index-patients 42.2 vs. family members 26.0 years). Six previously unreported disease-causing variants in the GLA gene were discovered. The nationwide screening and registration of Fabry disease families provide a unique possibility to establish a complete cohort of Fabry patients and to advance current knowledge of this inherited rare lysosomal storage disorder.
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spelling pubmed-96681182022-11-17 Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience Effraimidis, Grigoris Rasmussen, Åse Krogh Dunoe, Morten Hasholt, Lis F. Wibrand, Flemming Sorensen, Soren S. Lund, Allan M. Kober, Lars Bundgaard, Henning Yazdanfard, Puriya D. W. Oturai, Peter Larsen, Vibeke A. de Abreu, Vitor Hugo Fraga Enevoldsen, Lotte Hahn Kristensen, Tatiana Svenstrup, Kirsten Bille, Margrethe Bastholm Arif, Farah Mogensen, Mette Klokker, Mads Backer, Vibeke Kistorp, Caroline Feldt-Rasmussen, Ulla PLoS One Research Article The lysosomal storage disorder Fabry disease is caused by deficient or absent activity of the GLA gene enzyme α-galactosidase A. In the present study we present the molecular and biochemical data of the Danish Fabry cohort and report 20 years’ (2001–2020) experience in cascade genetic screening at the Danish National Fabry Disease Center. The Danish Fabry cohort consisted of 26 families, 18 index patients (9 males and 9 females, no available data for 8 index-patients) and 97 family members with a pathogenic GLA variant identified by cascade genetic testing (30 males and 67 females). Fourteen patients (5 males and 9 females; mean age of death 47.0 and 64.8 years respectively) died during follow-up. The completeness of the Fabry patient identification in the country has resulted in a cohort of balanced genotypes according to gender (twice number of females compared to males), indicating that the cohort was not biased by referral, and further resulted in earlier diagnosis of the disease by a lower age at diagnosis in family members compared to index-patients (mean age at diagnosis: index-patients 42.2 vs. family members 26.0 years). Six previously unreported disease-causing variants in the GLA gene were discovered. The nationwide screening and registration of Fabry disease families provide a unique possibility to establish a complete cohort of Fabry patients and to advance current knowledge of this inherited rare lysosomal storage disorder. Public Library of Science 2022-11-16 /pmc/articles/PMC9668118/ /pubmed/36383556 http://dx.doi.org/10.1371/journal.pone.0277767 Text en © 2022 Effraimidis et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Effraimidis, Grigoris
Rasmussen, Åse Krogh
Dunoe, Morten
Hasholt, Lis F.
Wibrand, Flemming
Sorensen, Soren S.
Lund, Allan M.
Kober, Lars
Bundgaard, Henning
Yazdanfard, Puriya D. W.
Oturai, Peter
Larsen, Vibeke A.
de Abreu, Vitor Hugo Fraga
Enevoldsen, Lotte Hahn
Kristensen, Tatiana
Svenstrup, Kirsten
Bille, Margrethe Bastholm
Arif, Farah
Mogensen, Mette
Klokker, Mads
Backer, Vibeke
Kistorp, Caroline
Feldt-Rasmussen, Ulla
Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience
title Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience
title_full Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience
title_fullStr Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience
title_full_unstemmed Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience
title_short Systematic cascade screening in the Danish Fabry Disease Centre: 20 years of a national single-centre experience
title_sort systematic cascade screening in the danish fabry disease centre: 20 years of a national single-centre experience
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668118/
https://www.ncbi.nlm.nih.gov/pubmed/36383556
http://dx.doi.org/10.1371/journal.pone.0277767
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