Hereditary Ataxia NGS panel

Genes
(full
coding region):		 ABCB7, ABHD12, ACO2, AFG3L2, AHI1, ANO10, APTX, ATCAY, ATG5, ATM, ATP1A2, ATP1A3, ATP8A2, ATP2B3, CA8, CACNA1A, CACNA1G, CACNB4, CAMTA1, CAPN1, CASK, CC2D2A, CCDC88C, CEP290, CHP1, CHRNA4, CLCN2, CLN5, COA7, COQ2, COQ4, COQ6, COQ7, COQ9, COQ8A, C9orf72, CPLANE1, CWF19L1, CYP27A1, DARS2, DEPDC5, DNMT1, EEF2, ELOVL4, ELOVL5, FAT2, FGF14, FLVCR1, FXN, GDAP2, GOSR2, GRID2, GRM1, GSS, GSX2, IFRD1, ITPR1, KCNA1, KCNC3, KCND3, KCNJ10, KCNMA1, KCNQ2, KIF1C, LAMA1, MAN2B1, MARS2, MECR, MME, MTCL1, MTPAP, NKX6-2, NOP56, NPC1, NPC2, OFD1, OPHN1, PAX6, PCDH12, PDSS1, PDSS2, PDYN, PEX7, PHYH, PNKD, PNKP, PNPLA6, POLG, PRKCG, RUBCN, PIK3R5, PLD3, PMPCA, POLR3A, POLR3B, PRRT2, PTF1A, PUM1, RNF216, SACS, SAMD9L, SCN1A, SCN2A, SCN8A, SCYL1, SERAC1, SETX, SIL1, SLC1A3, SLC16A2, SLC2A1, SLC25A46, SLC52A2, SLC9A1, SLC9A6, SNX14, SPG7, SPTBN2, SQSTM1, STUB1, SYNE1, SYT14, TDP2, TRPC3, TSFM, TTBK2, TDP1, TGM6, THG1L, TMEM231, TMEM240, TPP1, TTC19, TTPA, TUBB4A, TWNK, TXN2, UBA5, UBR4, VAMP1, VLDLR, VPS13D, VWA3B, WDR73, WDR81, WFS1, WWOX, XRCC1

List of diseases covered by the panel

The test is less informative for disease types (SCA1, SCA2, SCA3, SCA6, SCA7, SCA8, SCA12, SCA18) caused by triplet repeat expansion.
Non-coding variants: List of non-coding variants covered by the panel
Lab method: NGS panel with CNV analysis
TAT: 6-9 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

4 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Repeat Expansion Analysis Panel

Genes: ATXN1, ATXN2, ATXN3, ATXN7, ATXN8, ATXN10, ATN1, BEAN1, CACNA1A, FXN, NOP56, PPP2R2B, TBP
Lab method: Repeat expansion analysis
TAT: 4-6 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

2 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Repeat Expansion Analysis

Genes: ATXN1, ATXN2, ATXN3, ATXN7, CACNA1A
Lab method: Repeat expansion analysis
TAT: 4-6 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

2 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Repeat Expansion Analysis

Genes: FMR1
Lab method: Repeat expansion analysis
TAT: 4-6 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Mitochondrial genome sequencing

Lab method: Next generation sequencing
Heteroplasmy less than 20% is not detectable by sequencing.
TAT: 2-4 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Deletion/duplication analysis of selected regions

Lab method: Chromosomal Microarray Analysis
TAT: 2-4 weeks
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Indications for genetic testing:

1. Confirmation of clinical diagnosis
2. Differential diagnosis of hereditary ataxias and other genetically/phenotypically related disorders
3. Prenatal diagnosis for known familial mutation
5. Genetic counseling

The hereditary ataxias (HA) are a group of neurological disorders characterized by degenerative changes in the brain and spinal cord that lead to slowly progressive incoordination of gait, eye movements, speech, and hand movements, and frequently associated with atrophy of the cerebellum. Individual HA subtypes have variable age-of-onset (from infancy to adulthood). At present the classification of HA is based on the pattern of inheritance, causative gene, or chromosomal locus. Although, the nomenclature is still a work in progress because of the large number of subtypes and their broad phenotypic overlap.

By the test the most known genetic causes of hereditary ataxias are covered, but the sensitivity for certain disorders is variable.

The hereditary ataxias are inherited in an autosomal dominant, autosomal recessive, X-linked, or mitochondrial pattern.

The prevalence of individual subtypes of hereditary ataxias is not widely known and may vary from region to region, frequently because of founder effects.

References:

Bird TD. Hereditary Ataxia Overview. 1998 Oct 28 [Updated 2019 Jul 25]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020.  PMID: 20301317
Boycott KM, MacDonald SK, Parboosingh JS. VLDLR Cerebellar Hypoplasia. 2008 Aug 26 [Updated 2020 Feb 27]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. PMID: 20301729
Brkanac Z, Spencer D, Shendure J, et al. IFRD1 is a candidate gene for SMNA on chromosome 7q22-q23. Am J Hum Genet. 2009 May;84(5):692-7. doi: 10.1016/j.ajhg.2009.04.008. Epub 2009 Apr 30. PMID: 19409521
Brusco A, Di Gregorio E, Borroni B. Spinocerebellar Ataxia Type 38. 2019 Jul 11. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. PMID: 31294938
Chelban V, Kaya N, Alkuraya F, et al. NKX6-2-Related Disorder. 2018 Oct 4. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. PMID: 30285346
Chinnery PF. Mitochondrial Disorders Overview. 2000 Jun 8 [Updated 2014 Aug 14]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. PMID: 20301403
Coutinho P, Barbot C. Ataxia with Oculomotor Apraxia Type 1. 2002 Jun 11 [Updated 2015 Mar 19]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. PMID: 20301629