Invitae Hereditary Spastic Paraplegia Autosomal Dominant Panel

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  • Test code: 03261
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Test description

The Invitae Hereditary Spastic Paraplegia Autosomal Dominant Panel analyzes up to 16 genes that cause hereditary spastic paraplegia (HSP) that is inherited in an autosomal dominant pattern. These genes include the most common causes of autosomal dominant HSP: ATL1, K1F5A, REEP1, and SPAST.

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Primary panel (12 genes)

ALDH18A1 ATL1 BSCL2 HSPD1 KIAA0196 KIF1A KIF5A NIPA1 REEP1 RTN2 SPAST VAMP1

Add-on preliminary-evidence genes (4 genes)

Preliminary-evidence genes currently have early evidence of a clinical association with the specific disease covered by this test. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

CPT1C REEP2 SLC33A1 ZFYVE27

Alternative tests to consider

For a broader analysis, clinicians may consider the Invitae Hereditary Spastic Paraplegia Comprehensive panel. It includes genes with dominant, recessive, and X-linked inheritance and is particularly helpful if the inheritance is unclear. This broader panel can be ordered at no additional charge.

Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of neurological disorders that is subdivided into complicated (i.e., syndromic) and uncomplicated forms. All forms of HSP, complicated and uncomplicated, share the primary symptom of lower-extremity spastic weakness. Individuals with complicated HSP exhibit additional neurologic features such as intellectual disability, seizures, ataxia, peripheral neuropathy, deafness, cataracts, retinal degeneration, or muscle atrophy, depending on which gene is causative. Both HSP types are caused by the dysfunction of axons in the corticospinal tract that carry signals to the lower extremities. The majority of autosomal dominant HSP is uncomplicated, but complicated autosomal dominant forms also exist.

GeneSubtypeInheritanceClinical formAssociated syndromes and other related disorders
Autosomal dominantAutosomal recessiveX-linkedUncomplicatedComplicated
ALDH18A1 SPG9A, SPG9B
ATL1 SPG3A hereditary sensory neuropathy
BSCL2 SPG17 Silver syndrome, type-V; distal hereditary motor neuropathy; Charcot-Marie-Tooth disease, type-2; Berardinelli-Seip congenital lipodystrophy
CPT1C* SPG73
HSPD1 SPG13 MitCHAP-60 disease (leukodystrophy)
KIAA0196 SPG8 Ritscher-Schinzel syndrome 1
KIF1A SPG30
KIF5A SPG10
NIPA1 SPG6
REEP1 SPG31
REEP2* SPG72
RTN2 SPG12
SLC33A1* SPG42 congenital cataracts, hearing loss, and neurodegeneration
SPAST SPG4
VAMP1 SPAX1
ZFYVE27* SPG33

*Preliminary-evidence gene

This multi-gene panel analyzes up to 16 genes, including the most common genetic causes of autosomal dominant HSP: ATL1, K1F5A, REEP1, and SPAST. Other rare genes are also included on this panel, which increases the clinical sensitivity of this test, though the exact contribution of these additional genes to HSP is not known. In previous studies, the percent of families who received a genetic diagnosis after systematic testing ranged from 33% to 55% for autosomal dominant HSP.

This test is specific for subtypes of HSP that are inherited in an autosomal dominant pattern.

The penetrance of HSP varies depending on the causative gene and the specific pathogenic variant. Certain genes, such as HSPD1, REEP1, and SPAST, are known to have reduced penetrance and variable expression within a family. Average age of onset varies by gene and can occur at any time from early childhood to age 70.

The overall prevalence of HSP has been estimated at 1 in 10,000 to 1 in 100,000 people. The majority of HSP cases are inherited in an autosomal dominant pattern.

The clinical presentation of HSP can be variable. Genetic testing may confirm a suspected diagnosis or rule out disorders with similar symptoms. A genetic diagnosis can also help predict disease progression.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ALDH18A1 NM_002860.3
ATL1 NM_015915.4
BSCL2 NM_032667.6
CPT1C NM_001136052.2
HSPD1 NM_002156.4
KIAA0196 NM_014846.3
KIF1A NM_004321.6
KIF5A NM_004984.2
NIPA1 NM_144599.4
REEP1 NM_022912.2
REEP2 NM_001271803.1
RTN2 NM_005619.4
SLC33A1 NM_004733.3
SPAST NM_014946.3
VAMP1 NM_014231.3
ZFYVE27 NM_001002261.3