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Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study

Mucopolysaccharidoses (MPS) are a subgroup of 11 monogenic lysosomal storage disorders due to the deficit of activity of the lysosomal hydrolases deputed to the degradation of mucopolysaccharides. Although individually rare, all together they account for at least 1:25,000 live births. In this study,...

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Autores principales: Zanetti, Alessandra, D’Avanzo, Francesca, Rigon, Laura, Rampazzo, Angelica, Concolino, Daniela, Barone, Rita, Volpi, Nicola, Santoro, Lucia, Lualdi, Susanna, Bertola, Francesca, Scarpa, Maurizio, Tomanin, Rosella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459791/
https://www.ncbi.nlm.nih.gov/pubmed/30809705
http://dx.doi.org/10.1007/s00431-019-03341-8
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author Zanetti, Alessandra
D’Avanzo, Francesca
Rigon, Laura
Rampazzo, Angelica
Concolino, Daniela
Barone, Rita
Volpi, Nicola
Santoro, Lucia
Lualdi, Susanna
Bertola, Francesca
Scarpa, Maurizio
Tomanin, Rosella
author_facet Zanetti, Alessandra
D’Avanzo, Francesca
Rigon, Laura
Rampazzo, Angelica
Concolino, Daniela
Barone, Rita
Volpi, Nicola
Santoro, Lucia
Lualdi, Susanna
Bertola, Francesca
Scarpa, Maurizio
Tomanin, Rosella
author_sort Zanetti, Alessandra
collection PubMed
description Mucopolysaccharidoses (MPS) are a subgroup of 11 monogenic lysosomal storage disorders due to the deficit of activity of the lysosomal hydrolases deputed to the degradation of mucopolysaccharides. Although individually rare, all together they account for at least 1:25,000 live births. In this study, we present the genetic analysis of a population of 71 MPS patients enrolled in a multicenter Italian study. We re-annotated all variants, according to the latest recommendations, and re-classified them as suggested by the American College of Medical Genetics and Genomics. Variant distribution per type was mainly represented by missense mutations. Overall, 10 patients had received no molecular diagnosis, although 6 of them had undergone either HSCT or ERT, based on clinical and enzymatic evaluations. Moreover, nine novel variants are reported. Conclusions: Our analysis underlines the need to complete the molecular diagnosis in patients previously diagnosed only on a biochemical basis, suggests a periodical re-annotation of the variants and solicits their deposition in public databases freely available to clinicians and researchers. We strongly recommend a molecular diagnosis based on the analysis of the “trio” instead of the sole proband. These recommendations will help to obtain a complete and correct diagnosis of mucopolysaccharidosis, rendering also possible genetic counseling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00431-019-03341-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-64597912019-05-03 Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study Zanetti, Alessandra D’Avanzo, Francesca Rigon, Laura Rampazzo, Angelica Concolino, Daniela Barone, Rita Volpi, Nicola Santoro, Lucia Lualdi, Susanna Bertola, Francesca Scarpa, Maurizio Tomanin, Rosella Eur J Pediatr Original Article Mucopolysaccharidoses (MPS) are a subgroup of 11 monogenic lysosomal storage disorders due to the deficit of activity of the lysosomal hydrolases deputed to the degradation of mucopolysaccharides. Although individually rare, all together they account for at least 1:25,000 live births. In this study, we present the genetic analysis of a population of 71 MPS patients enrolled in a multicenter Italian study. We re-annotated all variants, according to the latest recommendations, and re-classified them as suggested by the American College of Medical Genetics and Genomics. Variant distribution per type was mainly represented by missense mutations. Overall, 10 patients had received no molecular diagnosis, although 6 of them had undergone either HSCT or ERT, based on clinical and enzymatic evaluations. Moreover, nine novel variants are reported. Conclusions: Our analysis underlines the need to complete the molecular diagnosis in patients previously diagnosed only on a biochemical basis, suggests a periodical re-annotation of the variants and solicits their deposition in public databases freely available to clinicians and researchers. We strongly recommend a molecular diagnosis based on the analysis of the “trio” instead of the sole proband. These recommendations will help to obtain a complete and correct diagnosis of mucopolysaccharidosis, rendering also possible genetic counseling. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00431-019-03341-8) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2019-02-26 2019 /pmc/articles/PMC6459791/ /pubmed/30809705 http://dx.doi.org/10.1007/s00431-019-03341-8 Text en © The Author(s) 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Article
Zanetti, Alessandra
D’Avanzo, Francesca
Rigon, Laura
Rampazzo, Angelica
Concolino, Daniela
Barone, Rita
Volpi, Nicola
Santoro, Lucia
Lualdi, Susanna
Bertola, Francesca
Scarpa, Maurizio
Tomanin, Rosella
Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study
title Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study
title_full Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study
title_fullStr Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study
title_full_unstemmed Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study
title_short Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study
title_sort molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459791/
https://www.ncbi.nlm.nih.gov/pubmed/30809705
http://dx.doi.org/10.1007/s00431-019-03341-8
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