Diagnosis; Drug Response; Mutation Confirmation; Prognostic

Establish or confirm diagnosis

Guidance for management

Lysosomal storage disorders are a family of disorders in which there is a pathological accumulation of macromolecules in the lysosomes. This may be the result of defects in lysosomal enzymefunction, or failure to transport across the lysosomal membrane. The accumulation of these macromolecules in turn result in cell damage and … Lysosomal storage disorders are a family of disorders in which there is a pathological accumulation of macromolecules in the lysosomes. This may be the result of defects in lysosomal enzymefunction, or failure to transport across the lysosomal membrane. The accumulation of these macromolecules in turn result in cell damage and ultimately impaired organ function.A list of more than 50 different inherited metabolic disorders fall under the category of lysosomal storage disorders. The London Health Sciences Centre Lysosomal Storage Panel (LHSC LSD) is a Next Generation Sequencing (NGS) test involving sequence and copy number analysis of coding regions and adjacent intronic regions for 53 genes associated with various forms of lysosomal storage disorders. The test is designed to provide rule out level assessment for all coding sequence and copy number alterations for 53 genes, which encompass the majority of the known genetic etiologies for lysosomal storage disorders. View more

All coding exons and 20 bp of flanking intronic sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; … All coding exons and 20 bp of flanking intronic sequence are enriched using an LHSC custom targeted hybridization protocol (Roche Nimblegen), followed by high throughput sequencing (Illumina). Sequence variants and copy number changes are assessed and interpreted using clinically validated algorithms and commercial software (SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual). All exons have >1000x mean read depth coverage, with a minimum 200x coverage at a single nucleotide resolution. This assay meets the sensitivity and specificity of combined Sanger sequencing and MLPA copy number analysis. All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely benign, benign) are not reported, but are available upon reques View more

Affymetrix CytoScan HD Array

Mutations identified are repeated in an independent assay using either Sanger sequence, MLPA, Q-PCR or other.

Tests performed
Entire test performed in-house

This assay meets the sensitivity and specificity of combined Sanger sequencing and MLPA copy number analysis, >99%

Is proficiency testing performed for this test? Help
Yes

Method used for proficiency testing: Help
Intra-Laboratory

Software used to interpret novel variations Help
SoftGenetics: Nextgene, Geneticist Assistant, Mutation Surveyor; and Alamut Visual with HGMD

Laboratory's policy on reporting novel variations Help
All variants interpreted as either ACMG category 1, 2, or 3 (pathogenic, likely pathogenic, VUS; PMID: 25741868) are confirmed using Sanger sequencing, MLPA, or other assays. ACMG category 4 and 5 variants (likely benign, benign) are not reported, but are available upon request