Hereditary Spastic Paraplegia NGS Panel

Turnaround Time

8 weeks

CPT Code(s)

81443

Cost

$3,500

Genes

• Spastic Paraplegia
• Adrenoleukodystrophy X-linked
• Peroxisomal acyl-CoA oxidase deficiency
• Aicardi-Goutieres syndrome
• Silver spastic paraplegia syndrome
• Pontocerebellar hypoplasia
• Intellectual Disability, X-linked syndromic, Claes-Jensen type
• Charcot-Marie-Tooth disease
• Rett syndrome
• 3-methylglutaconic aciduria
• Infantile neuroaxonal dystrophy
• Renpenning syndrome
• Warburg micro syndrome
• Neurodegen with brain iron accumulation
• Allan-Herndon-Dudley syndrome
• GLUT1 Deficiency
• Troyer syndrome
• Mast syndrome
• Cortical dysplasia with brain malformations
• Hypomyelinating leukodystrophy

This panel consists of 79 genes associated with hereditary spastic paraplegia, or HSP, which refers to a group of disorders associated with increased muscle tone, stiffness, and weakness in the lower extremities. In uncomplicated, also known as pure, spastic paraplegia, loss of sensation and overactive bladder may occur. Additional features including intellectual disability, gait abnormalities, seizures, dementia, and peripheral neuropathy, have been reported in cases that are considered to be complicated. The upper extremities are usually spared of symptoms. The prevalence of HSP is approximately 3 in 100,000, and an estimated 10% of patients have complicated HSP with additional clinical features. These conditions can be inherited in autosomal dominant, autosomal recessive, and X-linked dominant and recessive patterns, and each type exhibits variable clinical presentation, age of onset, degree of severity, and disease progression. Lifespan is typically unaffected. List of Genes and Conditions

Next Generation Sequencing

The current design of this panel covers all 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 and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts. We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution whole genome SNP microarray. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

The specimen should be kept at room temperature and delivered via overnight shipping. 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.

Prenatal diagnosis is available if the familial mutations are known. 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.