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Open Access 01-05-2019 | Original Article

Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study

Authors: Alessandra Zanetti, Francesca D’Avanzo, Laura Rigon, Angelica Rampazzo, Daniela Concolino, Rita Barone, Nicola Volpi, Lucia Santoro, Susanna Lualdi, Francesca Bertola, Maurizio Scarpa, Rosella Tomanin

Published in: European Journal of Pediatrics | Issue 5/2019

Abstract

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.

What is known
• MPS are a group of 11 metabolic genetic disorders due to deficits of enzymes involved in the mucopolysaccharides degradation.
• Molecular analysis is commonly performed to confirm enzymatic assays.
What is new
• Eighty-six percent of the 71 patients we collected received a molecular diagnosis; among them, 9 novel variants were reported.
• We stress the importance of molecular diagnosis in biochemically diagnosed patients, encourage a periodical re-annotation of variants according to the recent nomenclature and their publication in open databases.

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Title: Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study
Authors: Alessandra Zanetti
Francesca D’Avanzo
Laura Rigon
Angelica Rampazzo
Daniela Concolino
Rita Barone
Nicola Volpi
Lucia Santoro
Susanna Lualdi
Francesca Bertola
Maurizio Scarpa
Rosella Tomanin
Publication date: 01-05-2019
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Pediatrics / Issue 5/2019
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI: https://doi.org/10.1007/s00431-019-03341-8

At a glance: The STEP trials

Springer Medicine

Molecular diagnosis of patients affected by mucopolysaccharidosis: a multicenter study

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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