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Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2014

Open Access 01-12-2014 | Research

Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders

Authors: Ana Fernández-Marmiesse, Marcos Morey, Merce Pineda, Jesús Eiris, Maria Luz Couce, Manuel Castro-Gago, Jose Maria Fraga, Lucia Lacerda, Sofia Gouveia, Maria Socorro Pérez-Poyato, Judith Armstrong, Daisy Castiñeiras, Jose A Cocho

Published in: Orphanet Journal of Rare Diseases | Issue 1/2014

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Abstract

Background

With over 50 different disorders and a combined incidence of up to 1/3000 births, lysosomal storage diseases (LSDs) constitute a major public health problem and place an enormous burden on affected individuals and their families. Many factors make LSD diagnosis difficult, including phenotype and penetrance variability, shared signs and symptoms, and problems inherent to biochemical diagnosis. Developing a powerful diagnostic tool could mitigate the protracted diagnostic process for these families, lead to better outcomes for current and proposed therapies, and provide the basis for more appropriate genetic counseling.

Methods

We have designed a targeted resequencing assay for the simultaneous testing of 57 lysosomal genes, using in-solution capture as the enrichment method and two different sequencing platforms. A total of 84 patients with high to moderate-or low suspicion index for LSD were enrolled in different centers in Spain and Portugal, including 18 positive controls.

Results

We correctly diagnosed 18 positive blinded controls, provided genetic diagnosis to 25 potential LSD patients, and ended with 18 diagnostic odysseys.

Conclusion

We report the assessment of a next–generation-sequencing-based approach as an accessory tool in the diagnosis of LSDs, a group of disorders which have overlapping clinical profiles and genetic heterogeneity. We have also identified and quantified the strengths and limitations of next generation sequencing (NGS) technology applied to diagnosis.
Appendix
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Metadata
Title
Assessment of a targeted resequencing assay as a support tool in the diagnosis of lysosomal storage disorders
Authors
Ana Fernández-Marmiesse
Marcos Morey
Merce Pineda
Jesús Eiris
Maria Luz Couce
Manuel Castro-Gago
Jose Maria Fraga
Lucia Lacerda
Sofia Gouveia
Maria Socorro Pérez-Poyato
Judith Armstrong
Daisy Castiñeiras
Jose A Cocho
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2014
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/1750-1172-9-59

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