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

Orphanet Journal of Rare Diseases

Jose A Cocho²  Daisy Castiñeiras²  Judith Armstrong⁵  Maria Socorro Pérez-Poyato¹  Sofia Gouveia²  Lucia Lacerda⁴  Jose Maria Fraga²  Manuel Castro-Gago⁶  Maria Luz Couce²  Jesús Eiris⁶  Merce Pineda³  Marcos Morey²  Ana Fernández-Marmiesse² 

[1] Unidad de Neuropediatría. Hospital Clínico Universitario Marqués de Valdecilla, Santander, Spain;Unidad Diagnóstico y Tratamiento de Errores Congénitos del Metabolismo (Servicio de Neonatología), Facultad de Medicina y Odontología de la Universidad de Santiago de Compostela, 15706 Santiago de Compostela, La Coruña, Spain;Neuropediatra Fundación Hospital San Juan de Dios, CIBERER, Barcelona, Spain;Unidade de Bioquímica Genética, Centro de Genética Médica Jacinto Magalhães, Centro Hospitalar do Porto, Porto, Portugal;Servicio de Genética Molecular, Hospital San Juan de Dios, Barcelona, Spain;Servicio de Neuropediatría, Hospital Clínico Universitario de Santiago de Compostela, Facultad de Medicina y Odontología de la Universidad de Santiago de Compostela, Santiago de Compostela, La Coruña, Spain

关键词: Diagnostic odysseys;    Lysosomal storage disorders;    Targeted resequencing;    In-solution enrichment;   

Others  :  861970
DOI  :  10.1186/1750-1172-9-59

 received in 2013-10-16, accepted in 2014-04-07,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Fernández-Marmiesse et al.; licensee BioMed Central Ltd.

【 图 表 】

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