Spastic Paraplegia Panel

  • bpg-method PLUS
  • bpg-method SEQ
  • bpg-method DEL/DUP

Test code: NE0501

The Blueprint Genetics Spastic Paraplegia Panel is a 35 gene test for genetic diagnostics of patients with clinical suspicion of spastic paraplegia.

The panel covers genes for the nonsyndromic and syndromic hereditary spastic paraplegia (HSP), which is inherited in an autosomal recessive, autosomal dominant or X-linked manner. For patients with suspected amyotrophic lateral sclerosis, we offer Amyotrophic Lateral Sclerosis Panel.

About Spastic Paraplegia

HSP is a group of clinically and genetically heterogeneous neurodegenerative disorders characterized by lower extremity spasticity and weakness. If symptoms begin in very early childhood, they may be non-progressive and resemble spastic diplegic cerebral palsy. If symptoms begin later, they usually progress slowly and steadily. HSP is classified clinically as nonsyndromic (uncomplicated) or syndromic (complicated). Nonsyndromic HSPs are characterized by slowly progressive lower extremity spasticity and weakness, often associated with hypertonic urinary disturbances, mild reduction of lower extremity vibration sense and, occasionally, of joint position sensation. Syndromic HSP forms are characterized by the presence of additional neurological or non-neurological features. The prevalence of HSP is estimated to be 1-9 / 100 000.

Availability

Results in 3-4 weeks. We do not offer a maternal cell contamination (MCC) test at the moment. We offer prenatal testing only for cases where the maternal cell contamination studies (MCC) are done by a local genetic laboratory. Read more: http://blueprintgenetics.com/faqs/#prenatal

Genes in the Spastic Paraplegia Panel and their clinical significance
Gene Associated phenotypes Inheritance ClinVar HGMD
AFG3L2* Spastic ataxia, Spinocerebellar ataxia AD/AR 21 37
ALS2 Amyotrophic lateral sclerosis, Spastic paralysis AR 29 60
ATL1 Spastic paraplegia, Neuropathy, hereditary sensory AD 23 75
B4GALNT1 Spastic paraplegia AR 6 13
BSCL2 Lipodystrophy, congenital generalized, Encephalopathy, progressive AR 29 46
C12ORF65 Spastic paraplegia, Combined oxidative phosphorylation deficiency AR 10 10
C19ORF12 Spastic Paraplegia, Neurodegeneration with brain iron accumulation AR 16 36
CYP7B1 Bile acid synthesis defect AR 16 40
DDHD1 Spastic paraplegia AR 5 9
DDHD2 Spastic paraplegia AR 11 11
FA2H Spastic paraplegia AR 14 41
FXN* Friedreich ataxia AR 11 62
GALC Krabbe disease AR 66 233
GBA2 Cerebellar ataxia with spasticity AR 9 16
GJC2 Spastic paraplegia, Lymphedema, hereditary, Leukodystrophy, hypomyelinating AD/AR 22 54
HSPD1* Spastic paraplegia, Leukodystrophy, hypomyelinating AD/AR 4 4
KDM5C Mental retardation, syndromic, Claes-Jensen XL 36 48
KIAA0196 Spastic paraplegia, Ritscher-Schinzel syndrome (3C syndrome) AD/AR 9 16
KIF1A Spastic paraplegia, Neuropathy, hereditary sensory, Mental retardation AD/AR 52 35
KIF5A Spastic paraplegia AD 16 38
L1CAM Mental retardation, aphasia, shuffling gait, and adducted thumbs (MASA) syndrome, Hydrocephalus due to congenital stenosis of aqueduct of Sylvius, Spastic, CRASH syndrome, Corpus callosum, partial agenesis XL 57 286
MARS2 Combined oxidative phosphorylation deficiency AR 7 5
NIPA1 Spastic paraplegia AD 4 15
PLP1 Spastic paraplegia, Pelizaeus-Merzbacher disease XL 48 336
PNPLA6 Laurence-Moon syndrome, Boucher-Neuhauser syndrome AR 22 50
REEP1 Spastic paraplegia, Distal hereditary motor neuronopathy AD 14 57
SACS Spastic ataxia, Charlevoix-Saguenay AR 116 234
SETX Ataxia with oculomotor apraxia, Amyotrophic lateral sclerosis, juvenile, Spinocerebellar ataxia AD/AR 27 190
SLC16A2 Allan-Herndon-Dudley syndrome XL 30 81
SLC33A1* Congenital cataracts, hearing loss, and neurodegeneration AR 6 7
SPAST Spastic paraplegia AD 123 679
SPG7 Spastic paraplegia AR 53 104
SPG11 Spastic paraplegia, Amyotrophic lateral sclerosis, Charcot-Marie-Tooth disease AR 129 254
SPG20 Spastic paraplegia (Troyer syndrome) AR 6 4
SPR Dystonia, Dopa-responsive, due to sepiapterin reductase deficiency AR 11 22

*Some regions of the gene are duplicated in the genome leading to limited sensitivity within the regions. Thus, low-quality variants are filtered out from the duplicated regions and only high-quality variants confirmed by other methods are reported out. Read more.

Gene, refers to HGNC approved gene symbol; Inheritance to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL); ClinVar, refers to a number of variants in the gene classified as pathogenic or likely pathogenic in ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/); HGMD, refers to a number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/). The list of associated (gene specific) phenotypes are generated from CDG (http://research.nhgri.nih.gov/CGD/) or Orphanet (http://www.orpha.net/) databases.

Gene Genomic location HG19 HGVS RefSeq RS-number
GJC2 Chr1:228337561 c.-167A>G NM_020435.3
GJC2 Chr1:228337558 c.-170A>G NM_020435.3
L1CAM ChrX:153131293 c.2432-19A>C NM_000425.4

The strengths of this test include:

  • Blueprint Genetics is one of the few laboratories worldwide with CAP and ISO-15189 accreditation for NGS panels and CLIA certification
  • Superior sequencing quality
  • Careful selection of genes based on current literature, our experience and the most current mutation databases
  • Transparent and easy access to quality and performance data at the patient level that are accessible via our Nucleus portal
  • Transparent and reproducible analytical validation for each panel (see Test performance section; for complete details, see our Analytic Validation)
  • Sequencing and high resolution del/dup analysis available in one test
  • Inclusion of non-coding disease causing variants where clinically indicated (please see individual Panel descriptions)
  • Interpretation of variants following ACMG variant classification guidelines
  • Comprehensive clinical statement co-written by a PhD geneticist and a clinician specialist

 

This test does not detect the following:

  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Mitochondrial DNA variants
  • Variants in regulatory or non-coding regions of the gene unless otherwise indicated (please see Non-coding disease causing variants covered by the panel). This mean for instance intronic variants locating deeper than 15 nucleotides from the exon-intron boundary.

 

This test may not reliably detect the following:

  • Low level mosaicism
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments
  • Disorders caused by long repetitive sequences (e.g. trinucleotide repeat expansions)

 

The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.

For additional information, please refer to the Test performance section and see our Analytic Validation.

Blueprint Genetics offers a comprehensive Spastic Paraplegia Panel that covers classical genes associated with spastic paraplegia. The genes are carefully selected based on the existing scientific evidence, our experience and most current mutation databases. Candidate genes are excluded from this first-line diagnostic test. The test does not recognise balanced translocations or complex inversions, and it may not detect low-level mosaicism. The test should not be used for analysis of sequence repeats or for diagnosis of disorders caused by mutations in the mitochondrial DNA.

Analytical validation is a continuous process at Blueprint Genetics. Our mission is to improve the quality of the sequencing process and each modification is followed by our standardized validation process. Average sensitivity and specificity in Blueprint NGS Panels is 99.3% and 99.9% for detecting SNPs. Sensitivity to for indels vary depending on the size of the alteration: 1-10bps (96.0%), 11-20 bps (88.4%) and 21-30 bps (66.7%). The longest detected indel was 46 bps by sequence analysis. Detection limit for Del/Dup (CNV) analysis varies through the genome depending on exon size, sequencing coverage and sequence content. The sensitivity is 71.5% for single exon deletions and duplications and 99% for three exons’ deletions and duplications. We have validated the assays for different starting materials including EDTA-blood, isolated DNA (no FFPE) and saliva that all provide high-quality results. The diagnostic yield varies substantially depending on the used assay, referring healthcare professional, hospital and country. Blueprint Genetics’ Plus Analysis (Seq+Del/Dup) maximizes the chance to find molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be cost-effective first line test if your patient’s phenotype is suggestive for a specific mutation profile.

The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. The highest relevance in the reported variants is achieved through elimination of false positive findings based on variability data for thousands of publicly available human reference sequences and validation against our in-house curated mutation database as well as the most current and relevant human mutation databases. Reference databases currently used are the 1000 Genomes Project (http://www.1000genomes.org), the NHLBI GO Exome Sequencing Project (ESP; http://evs.gs.washington.edu/EVS), the Exome Aggregation Consortium (ExAC; http://exac.broadinstitute.org), ClinVar database of genotype-phenotype associations (http://www.ncbi.nlm.nih.gov/clinvar) and the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk). The consequence of variants in coding and splice regions are estimated using the following in silico variant prediction tools: SIFT (http://sift.jcvi.org), Polyphen (http://genetics.bwh.harvard.edu/pph2/), and Mutation Taster (http://www.mutationtaster.org).

Through our online ordering and statement reporting system, Nucleus, the customer can access specific details of the analysis of the patient. This includes coverage and quality specifications and other relevant information on the analysis. This represents our mission to build fully transparent diagnostics where the customer gains easy access to crucial details of the analysis process.

In addition to our cutting-edge patented sequencing technology and proprietary bioinformatics pipeline, we also provide the customers with the best-informed clinical report on the market. Clinical interpretation requires fundamental clinical and genetic understanding. At Blueprint Genetics our geneticists and clinicians, who together evaluate the results from the sequence analysis pipeline in the context of phenotype information provided in the requisition form, prepare the clinical statement. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals, even without training in genetics.

Variants reported in the statement are always classified using the Blueprint Genetics Variant Classification Scheme modified from the ACMG guidelines (Richards et al. 2015), which has been developed by evaluating existing literature, databases and with thousands of clinical cases analyzed in our laboratory. Variant classification forms the corner stone of clinical interpretation and following patient management decisions. Our statement also includes allele frequencies in reference populations and in silico predictions. We also provide PubMed IDs to the articles or submission numbers to public databases that have been used in the interpretation of the detected variants. In our conclusion, we summarize all the existing information and provide our rationale for the classification of the variant.

A final component of the analysis is the Sanger confirmation of the variants classified as likely pathogenic or pathogenic. This does not only bring confidence to the results obtained by our NGS solution but establishes the mutation specific test for family members. Sanger sequencing is also used occasionally with other variants reported in the statement. In the case of variant of uncertain significance (VUS) we do not recommend risk stratification based on the genetic finding. Furthermore, in the case VUS we do not recommend use of genetic information in patient management or genetic counseling. For some cases Blueprint Genetics offers a special free of charge service to investigate the role of identified VUS.

We constantly follow genetic literature adapting new relevant information and findings to our diagnostics. Relevant novel discoveries can be rapidly translated and adopted into our diagnostics without delay. These processes ensure that our diagnostic panels and clinical statements remain the most up-to-date on the market.

Find more info in Support

Choose an analysis method

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$ $ 1000
$ $ 1900

Extra services

$ 500
Total $
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ICD & CPT codes

CPT codes

SEQ 81479
DEL/DUP 81479


ICD codes

Commonly used ICD-10 codes when ordering the Spastic Paraplegia Panel

ICD-10 Disease
G11.4 Spastic paraplegia

Accepted sample types

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 5μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.

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