NGS Neuronal Ceroid Lipofuscinoses Panel
Neuronal Ceroid Lipofuscinoses
The neuronal ceroid-lipofuscinoses (NCLs) are a genetically heterogenous group of neurodegenerative lysosomal storage disorders. While most are autosomal recessive, there is at least one autosomal dominant NCL. The severity and phenotype varies within this group of disorders, but almost all are characterized by progressive cognitive and motor deterioration as well as seizures. Vision loss, developmental delay, ataxia, intellectual disability, and early death are also common within the group of NCLs. Age of onset can range from infantile to childhood to adult onset.
|Indications||The clinical presentation for many of the neuronal ceroid lipofuscinoses can be similar. This panel may be useful in identifying the specific underlying genetic etiology.
For patients with a specific suspected NCL, enzyme analysis or individual gene sequencing should be considered first.
|Detection||The current design of the neuronal ceroid lipofuscinosis panel covers the coding region for all 9 genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. All novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations.
We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution testing whole genome SNP microarray. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.
||Effective January 1, 2017, all NGS panels are performed on an exome backbone with the potential for reflex to whole exome sequencing at a reduced cost. Please contact the laboratory to discuss the requirements for exome sequencing.|
|Specimen Requirements||5 to 10 ml of peripheral blood collected in an EDTA (lavender top) Vacutainer tube is preferred. The minimal blood needed for reliable DNA isolation is 3 ml.|
|Transport||The specimen should be kept at room temperature and delivered via overnight shipping. FedEx is preferred. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.|
|Turnaround time||8-10 weeks|
|Prenatal testing||If the pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies. Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.|
Insurance billing is available for this test. The Insurance Billing Form is required along with copies of the authorization or letter of agreement from the insurance company.
Molecular Diagnostic Lab
The Molecular Diagnostic Lab offers DNA analysis for many genetic disorders via gene sequencing, targeted mutation analysis, MLPA deletion/duplication testing, trinucleotide repeat analysis and next generation sequencing panels.