Test code: NE2101
The Blueprint Genetics Ataxia Panel is a 141 gene test for genetic diagnostics of patients with clinical suspicion of cerebellar ataxia, episodic ataxia or spinocerebellar ataxia.
Hereditary ataxia can be inherited in an autosomal recessive, autosomal dominant or X-linked manner. The clinical utility of a multi-gene panel for diagnosis of hereditary ataxias has been shown to be efficient, cost effective and enabled a molecular diagnosis in many refractory cases (PMID: 24030952). By sequencing 58 known human ataxia genes in 50 heterogeneous patients with ataxia who had been extensively investigated and were refractory to diagnosis, the overall detection rate of 18% was achieved. It was 40% in those with a childhood or adolescent onset progressive disorder and 75% in those with an adolescent onset and a family history.
The hereditary ataxias are a group of genetic disorders characterized by slowly progressive incoordination of gait and often associated with poor coordination of hands, speech, and eye movements. Frequently, atrophy of the cerebellum occurs. The episodic ataxias are characterized by periods of unsteady gait often associated with nystagmus or dysarthria. Myokymia, vertigo, or hearing loss may occur in some of the subtypes. Permanent ataxia and even cerebellar atrophy may result late in the disease course. Prevalence of the autosomal dominant cerebellar ataxias (ADCAs) is estimated to be approximately 1-5:100,000. Often, one autosomal dominant ataxia cannot be differentiated from another because the most frequent manifestations of all of AD ataxias are progressive adult-onset gait ataxia and dysarthria associated with cerebellar atrophy on brain imaging; secondly, the ages of onset often overlap. Most ADCAs are spinocerebellar ataxias (SCA) or episodic ataxias. Autosomal recessive types of hereditary ataxia account for approximately 3:100,000 with Friedreich ataxia, ataxia-telangiectasia, and ataxia oculomotor apraxia being most common. Most of the spastic ataxias are recessively inherited.
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
|ABCB7||Anemia, sideroblastic, and spinocerebellar ataxia||XL||8||9|
|ABHD12||Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract||AR||12||18|
|ACO2||Optic atrophy, Infantile cerebellar-retinal degeneration||AR||13||13|
|ADCK3||Coenzyme Q10 deficiency, Progressive cerebellar ataxia and atrophy, Spinocerebellar ataxia||AR||40||37|
|AFG3L2*||Spastic ataxia, Spinocerebellar ataxia||AD/AR||21||37|
|ALDH5A1||Succinic semialdehyde dehydrogenase deficiency||AR||10||69|
|APTX||Ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia||AR||14||40|
|ARL6||Bardet-Biedl syndrome, Retinitis pigmentosa||AR||13||21|
|ATCAY||Ataxia, cerebellar, Cayman||AR||1||2|
|ATM||Breast cancer, Ataxia-Telangiectasia||AD/AR||646||923|
|ATXN3||Spinocerebellar ataxia (Machado-Joseph disease)||AD||2||3|
|BBS2||Bardet-Biedl syndrome, Retinitis pigmentosa||AR||32||90|
|C5ORF42||Orofaciodigital syndrome, Joubert syndrome||AR||68||98|
|C10ORF2||Perrault syndrome, Mitochondrial DNA depletion syndrome||AR||37|
|CA8||Cerebellar ataxia, mental retardation, and dysequilibrium syndrome||AR||2||4|
|CACNA1A||Migraine, familial hemiplegic, Episodic ataxia||AD||93||203|
|CAMTA1||Cerebellar ataxia, nonprogressive, with mental retardation||AD||27||7|
|CASK||Mental retardation and microcephaly with pontine and cerebellar hypoplasia, FG syndrome, Mental retardation||XL||67||87|
|CC2D2A||COACH syndrome, Joubert syndrome, Meckel syndrome||AR||71||86|
|CCDC28B||Bardet-Biedl syndrome, modifier||AD|
|CEP290*||Bardet-Biedl syndrome, Leber congenital amaurosis, Joubert syndrome, Senior-Loken syndrome, Meckel syndrome||AR||96||266|
|CLCN2||Leukoencephalopathy with ataxia, Epilepsy||AD/AR||19||22|
|CLN5||Neuronal ceroid lipofuscinosis, type 5||AR||47||43|
|COX20||Mitochondrial complex IV deficiency||AR||4||1|
|CSTB||Epilepsy, progressive myoclonic||AR||17||15|
|DNMT1||Neuropathy, hereditary sensory, Cerebellar ataxia, deafness, and narcolepsy||AD||10||19|
|ELOVL4||Stargardt disease, Icthyosis, spastic quadriplegia, and mental retardation, Spinocerebellar ataxia||AD/AR||10||12|
|FBXL4||Mitochondrial DNA depletion syndrome||AR||54||36|
|FLVCR1||Ataxia, posterior column, with retinitis pigmentosa||AR||6||15|
|FMR1||Premature ovarian failure||XL||13||76|
|GBA2||Cerebellar ataxia with spasticity||AR||9||16|
|GOSR2*||Epilepsy, progessive myoclonic||AR||5||2|
|GSS||Glutathione synthetase deficiency||AR||7||34|
|INPP5E||Joubert syndrome, Mental retardation, truncal obesity, retinal dystrophy, and micropenis (MORM syndrome)||AR||23||44|
|ITM2B||Dementia, familial Danish, Retinal dystrophy with inner retinal dysfunction and ganglion cell abnormalities, Cerebral amyloid angiopathy||AD||3||3|
|KCNA1||Episodic ataxia/myokymia syndrome||AD||22||40|
|KCNJ10||Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SESAME syndrome), Pendred syndrome, Enlarged vestibular aqueduct||AR/Digenic||14||24|
|KIF7||Acrocallosal syndrome, Hydrolethalus syndrome, Al-Gazali-Bakalinova syndrome, Joubert syndrome||AR/Digenic||15||40|
|MARS2||Combined oxidative phosphorylation deficiency||AR||7||5|
|MKKS||Bardet-Biedl syndrome, McKusick-Kaufman syndrome||AR||15||59|
|MKS1||Bardet-Biedl syndrome, Meckel syndrome||AR||42||51|
|NOL3||Myoclonus, familial cortical||AD||1||2|
|NPHP1||Nephronophthisis, Joubert syndrome, Senior-Loken syndrome||AR||14||73|
|OFD1||Simpson-Golabi-Behmel syndrome, Retinitis pigmentosa, Orofaciodigital syndrome, Joubert syndrome||XL||133||156|
|OPHN1||Mental retardation, with cerebellar hypoplasia and distinctive facial appearance||XL||23||35|
|PAX6||Aniridia, cerebellar ataxia, and mental retardation (Gillespie syndrome), Keratitis, Coloboma, ocular, Cataract with late-onset corneal dystrophy, Morning glory disc anomaly, Foveal hypoplasia, Aniridia, Optic nerve hypoplasia, Peters anomaly||AD||106||473|
|PEX7||Refsum disease, Rhizomelic CDP type 1||AR||36||52|
|PNKD||Paroxysmal non-kinesigenic dyskinesia||AD||4||3|
|PNKP||Epileptic encephalopathy, early infantile, Ataxia-oculomotor||AR||31||17|
|PNPLA6||Laurence-Moon syndrome, Boucher-Neuhauser syndrome||AR||22||50|
|POLG||POLG-related ataxia neuropathy spectrum disorders, Sensory ataxia, dysarthria, and ophthalmoparesis, Alpers syndrome, Progressive external ophthalmoplegia with mitochondrial DNA deletions, Mitochondrial DNA depletion syndrome||AD/AR||92||274|
|PRRT2||Episodic kinesigenic dyskinesia||AD||33||93|
|RPGRIP1L||COACH syndrome, Joubert syndrome, Meckel syndrome, Retinal degeneration in ciliopathy, modifier||AD/AR||35||45|
|SACS||Spastic ataxia, Charlevoix-Saguenay||AR||116||234|
|SETX||Ataxia with oculomotor apraxia, Amyotrophic lateral sclerosis, juvenile, Spinocerebellar ataxia||AD/AR||27||190|
|SLC2A1||Stomatin-deficient cryohydrocytosis with neurologic defects, Epilepsy, idiopathic generalized, GLUT1 deficiency syndrome||AD/AR||82||259|
|SLC9A6||Mental retardation, syndromic, Christianson||XL||22||19|
|SLC52A2||Brown-Vialetto-Van Laere syndrome||AR||22||19|
|TCTN2||Joubert syndrome, Meckel syndrome||AR||17||13|
|TCTN3||Orofaciodigital syndrome (Mohr-Majewski syndrome), Joubert syndrome||AR||9||10|
|TDP1||Spinocerebellar ataxia, with axonal neuropathy||AR||1||2|
|TMEM67||Nephronophthisis, COACH syndrome, Joubert syndrome, Meckel syndrome||AR||82||153|
|TMEM216||Joubert syndrome, Meckel syndrome||AR||14||8|
|TMEM231||Joubert syndrome, Meckel syndrome||AR||9||19|
|TPP1||Spinocerebellar ataxia, Neuronal ceroid lipofuscinosis type 2||AR||52||110|
|TRIM32||Bardet-Biedl syndrome, Muscular dystrophy, limb-girdle||AR||11||16|
|TTC8||Bardet-Biedl syndrome, Retinitis pigmentosa||AR||5||16|
|TTPA||Ataxia with isolated vitamin E deficiency||AR||26||28|
|TUBB4A*||Leukodystrophy, hypomyelinating, Dystonia||AD||38||38|
|VLDLR||Cerebellar ataxia, mental retardation, and dysequilibrium syndrome||AR||9||24|
|WDPCP||Meckel-Gruber syndrome, modifier, Bardet-Biedl syndrome, Congenital heart defects, hamartomas of tongue, and polysyndactyly||AR||6||7|
|WFS1||Wolfram syndrome, Deafness||AD/AR||65||343|
|WWOX||Epileptic encephalopathy, early infantile, Spinocerebellar ataxia||AR||30||36|
|ZNF423||Nephronophthisis, Joubert syndrome||AD/AR||10||7|
*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|
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 Ataxia Panel that covers classical genes associated with cerebellar ataxia, episodic ataxia and spinocerebellar ataxia. 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.
Choose an analysis method
ICD & CPT codes
Commonly used ICD-10 codes when ordering the Ataxia Panel
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.