An interventional study of NGS-based genetic testing in Lysosomal Storage Diseases, sponsored by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico. Active, not recruiting at 1 site in Italy. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-07.
Sponsored by Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico · Not applicable, Interventional, and Diagnostic
LYSO-NEXT uses genetic sequencing to identify undiagnosed lysosomal storage disorders in adults with unexplained neurological symptoms. Participants undergo whole-exome sequencing, which examines the protein-coding regions of DNA. A small subgroup with inconclusive results and strong clinical suspicion undergoes additional long-read sequencing to detect genetic changes that may be missed by the initial test. The study assesses the proportion of participants diagnosed with a lysosomal storage disorder and the diagnostic yield of each sequencing approach.
Participants undergo clinical assessment, pre-test genetic counseling, and a single blood collection for DNA extraction. Whole-exome sequencing data are initially analyzed using a virtual panel of lysosomal storage disorder genes; if no diagnosis is established, analysis is extended to other genes. Identified variants are confirmed by Sanger sequencing.
Approximately 10 selected participants undergo long-read sequencing to investigate structural variants. Selection focuses on unresolved cases with a single pathogenic variant in a gene associated with an autosomal recessive disorder or a strongly suggestive phenotype despite negative first-line testing.
Genetic findings guide clinical reassessment to evaluate genotype-phenotype compatibility. Participants who choose to receive their results are offered a genetic report and post-test counseling.
62 studies on the registry are indexed under Lysosomal Storage Diseases; 14 are open to participants now.
This study's enrollment of 1,000 is above the median of 12 across 31 interventional studies indexed under Lysosomal Storage Diseases.
Browse Lysosomal Storage Diseases studies →Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico is the lead sponsor of 232 studies on the registry; 83 are open to participants now.
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Exclusion Criteria:
- Neurological signs and symptoms definitively attributable to acquired causes, including trauma, tumors, infections, or acquired metabolic conditions.
Adults with neurological manifestations and no established genetic diagnosis undergo pre-test counseling, a single venous blood collection, and first-line whole-exome sequencing. Approximately 10 selected participants undergo additional long-read sequencing using the same sample. Genetic findings are followed by clinical reassessment and, for participants who choose to receive results, a genetic report and post-test counseling.
Diagnostic Test: NGS-based genetic testing
A single peripheral venous blood collection (two 7 mL EDTA tubes) is used for DNA extraction and whole-exome sequencing in all participants. First-line analysis uses the Nextera Exome Library protocol and Illumina NextSeq500 platform, followed by bioinformatic analysis for causal variants. Approximately 10 selected participants with unresolved findings and strong suspicion of a lysosomal storage disorder undergo second-line long-read sequencing without an additional blood collection. Testing is preceded by genetic counseling and followed by clinical reassessment and, for participants who choose to receive results, a genetic report and post-test counseling. The genetic analysis phase is expected to last approximately six months.
Prevalence of genetically diagnosed lysosomal storage disorders
Proportion of enrolled participants with a genetically diagnosed lysosomal storage disorder, calculated as the number of participants diagnosed with a lysosomal storage disorder divided by the total number of participants recruited. Genetic findings are assessed together with clinical reassessment to establish genotype-phenotype compatibility.
Time frame: At completion of genetic analysis and clinical reassessment, approximately 6 months after blood sampling
Diagnostic yield of whole-exome sequencing
Proportion of participants receiving a genetic diagnosis through whole-exome sequencing (WES), calculated as the number of cases diagnosed by WES divided by the number of cases sequenced using WES.
Time frame: At completion of whole-exome sequencing analysis and clinical reassessment, approximately 6 months after blood sampling
Diagnostic yield of long-read next-generation sequencing
Proportion of selected participants receiving a genetic diagnosis through long-read next-generation sequencing, calculated as the number of cases diagnosed by long-read sequencing divided by the number of cases sequenced using this approach. This analysis is performed in approximately 10 highly selected participants whose first-line short-read analysis has not established a complete diagnosis.
Time frame: At completion of long-read sequencing analysis and clinical reassessment, expected approximately 6 months after blood sampling
Plan to share: Undecided
Ran from May 2024 to primary completion in Sep 2026, 28 months.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is active, not recruiting, as verified in Oct 2026. You cannot join it, but the record below documents what was studied.
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