Genetic testing for inherited movement disorders

This website provides suggestions on genetic testing from movement disorders from the Australian perspective. We provide a suggested list of laboratories where genetic testing can be performed. We work closely with our clinical genetics service to decide whether genetic testing is warranted and the most cost effective way to go about it.

The list of laboratories is not an exhaustive list of the laboratories that provide such testing. A referral to a specialist neurogenetics and/or clinical genetics service and clinical genetics counselling should also be considered.

The Movement Disorder Society of Australia and New Zealand (MDSANZ) does not accept responsibility for, and makes no representation concerning, the accuracy, appropriateness, and completeness of the information contained on the following pages. MDSANZ does not provide any direct or implied endorsement of the tests or laboratories listed, and accepts no responsibility for the information provided. It is recommended that genetic testing be performed in an accredited laboratory, and it should be emphasised that the listing of a test or laboratory on this page does not imply that it has been accredited by NATA or any other organisation. Note that charges may apply for gene tests and enquiries about charges should be made to the laboratory to which a sample is to be referred prior to referral. Users access the linked websites at their own risk. Please note that other websites for genetic testing are available (e.g. http://genetictesting.rcpa.edu.au/)

Hereditary spastic paraplegia (HSP) is inherited condition characterised by progressive stiffness in the lower limbs. There are over 60 genes involved which makes genetic testing particularly challenging. HSP can be categorised as either 'pure' or 'complicated'.

It is worth noting that in Australia the most common cause of HSP is SPG4, accounting for over 50% of cases (Vandebona et al., SPAST mutations in Australian patients with hereditary spastic paraplegia, 2012). SPG4 is typically associated with pure forms of HSP or those with a family history consistent with autosomal dominant inheritance. Multiplex Ligation-dependent Probe Amplification (MLPA) should also be considered to detect deletions in the SPAST gene. SPG3A is thought to be a common cause of early onset HSP, and SPG31 is the third most common cause of autosomal dominant HSP.

In terms of autosomal recessive HSP, the SPG11 and SPG15 forms should be considered if there is evidence of a thin corpus callosum on MRI brain. SPG7 and SPG5 are also frequent in Australia (Kumar et al., Targeted next generation sequencing in SPAST-negative hereditary spastic paraplegia, 2013).

For more detailed review regarding genetic testing in HSP, please see the following papers (Fink, Hereditary Spastic Paraplegia Overview, 2000; Kumar et al., An Update on the Hereditary Spastic Paraplegias: New genes and New Disease Models, 2015).

Molecular Medicine Laboratory, Concord Repatriation General Hospital

Website: http://www.slhd.nsw.gov.au/sswps/crgh/molmedicine/gene_molmed.pdf
Mail: Molecular Medicine Laboratory, Clinical Sciences Building Concord Hospital, NSW 2139, Australia
Phone: +61297677009
Fax: +61297676194
Email: molmed@med.usyd.edu.au
Test types
Sanger sequencing: SPG4, SPG3A, SPG31
MLPA: SPG4, SPGA3A, SPG31
Whole exome sequencing: HSP exome

PathWest Laboratory Medicine

Website: https://pathwest.health.wa.gov.au/Services/ClinicalServices/Genetics/Pages/Diagnostic%20Genomics.aspx
Mail: Neurogenetics Unit, Department of Diagnostic Genomics, PathWest Laboratory Medicine WA, Level 2, PP Building, QEII Medical Centre, Hospital Avenue, Nedlands WA 6009
Phone: +61863834219
Fax No.: +61893464029
Test type
Next generation sequencing panel: AFG3L2, ABCD1, ALDH3A2, ALS2, AMPD2, AP4B1, AP4E1, AP4M1, AP4S1, AP5Z1, ARL6IP1, ARSI, ATL1, ATP2B4, ATP6AP2, B4GALNT1, BSCL2, C12ORF65, C19ORF12, CCT4, CYP7B1, DDHD1, DDHD2, ENTPD1, ERLIN1, ERLIN2, FA2H, FLRT1, CYP2U1, GAD1, GBA2, GJC2, HSPD1, KIAA0196, KIF1A, KIF1C, KIF5A, L1CAM, LYST, MAG, MARS, MARS2, MTPAP, NIPA1, NT5C2, PGAP1, PLP1, PNPLA6, RAB3GAP2, REEP1, REEP2, RTN2, SACS, SLC16A2, SLC33A1, SPAST, SPG11, SPG20, SPG21, SPG7, STUB1, TECPR2, TFG, USP8, VAMP1, VPS37A, WDR48, ZFR, ZFYVE26, ZFYVE27

Sheffield Diagnostic Genetics Service (SDGS)

Website: https://www.sheffieldchildrens.nhs.uk/downloads/labgenetics/LabGenetics_NGSNDTests.pdf
Mail: Sheffield Diagnostic Genetics Service (SDGS) Sheffield Children's NHS Foundation Trust Western Bank SHEFFIELD S10 2TH
Phone: + 44(0) 114 271 7003
Fax: + 44(0) 114 275 0629
Email: SDGS@sch.nhs.uk
Test Type
Next generation sequencing panel: AFG3L2, ALS2, AP5Z1, ATL1, B4GALNT1, BSCL2, C12orf65, CYP27A1, CYP2U1, CYP7B1, DDHD1, DDHD2, FA2H, FIG4, GBA2, HSPD1, KIAA0196, KIF1A, KIF5A, L1CAM, MTPAP, NIPA1, PLP1, PSEN1, REEP1, RTN2, SACS, SIGMAR1, SLC16A2, SLC2A1, SPAST, SPG11, SPG20, SPG21, SPG7, VAMP1, VPS37A, WDR45, ZFYVE26, ZFYVE27

Centogene

Website: https://www.centogene.com/genetic-testing/genetic-test-methods/next-generation-sequencing.html
Mail: CENTOGENE AG Schillingallee 68 18057 Rostock, Germany
Phone: +49 (0)381 203 652- 222
Fax: +49 (0)381 203 652-119
Email: dmqc@centogene.com
Test types
Next generation sequencing panel (complete): ALDH18A1, ALS2, AMPD2, AP4B1, AP4E1, AP4M1, AP4S1, AP5Z1, ARL6IP1, ARSI, ATL1, ATP2B4, B4GALNT1, BICD2, BSCL2, C12ORF65, C19orf12, CCT5, CYP2U1, CYP7B1, DDHD1, DDHD2, ENTPD1, ERLIN1, ERLIN2, EXOSC3, FA2H, FLRT1, GBA2, GJC2, HSPD1, KIAA0196, KIF1A, KIF1C, KIF5A, L1CAM, MAG, MARS, NIPA1, NT5C2, PGAP1, PLP1, PNPLA6, RAB3GAP2, REEP1, REEP2, RTN2, SACS, SLC16A2, SLC33A1, SPAST, SPG11, SPG20, SPG21, SPG7, TECPR2, TFG, TTR, USP8, VAMP1, VPS37A, WDR48, ZFR, ZFYVE26, ZFYVE27
Deletion/Duplication testing: NIPA1, REEP1, SACS, PLP1, SPG7, ATL1, SPG11, SPAST, L1CAM
NGS panel autosomal dominant
NGS panel autosomal recessive
Whole exome sequencing
Whole genome sequencing

Genome.One

Website: https://www.genome.one/
Mail: Genome.One
370 Victoria St
Darlinghurst, NSW 2010
Sydney, Australia
Phone: +61 2 9359 8002
Fax: +61 2 9359 8033
Email: clinical@genome.one
Test type
Clinical Whole Genome Sequencing

The inherited ataxias are a highly heterogeneous group of neurological disorders with many subtypes and extensive phenotypic overlap:

• Spinocerebellar ataxia (SCA) refers to autosomal dominant hereditary ataxia, many of which are CAG trinucleotide repeat expansion disorders.

• SCAR refers to spinocerebellar ataxia autosomal recessive.

• EA refers to episodic ataxias.

• SPAX refers to ataxias that often have a prominent component of spasticity.

Please also consider Freidreich ataxia (FRDA) which is one of the most common forms of inherited ataxia. FRDA is usually associated with dysarthria, muscle weakness, lower limb spasticity, scoliosis, bladder dysfunction, absent lower limb reflexes, and loss of position and vibration sense (Bidichandani & Delatycki, Friedreich Ataxia, 1998). Fragile X tremor ataxia syndrome should also be considered.

After excluding spinocerebellar ataxia 1-3, 6, 7 and Friedrich's ataxia, next generation sequencing panels can be expected to detect a cause in about 18% of cases (Nemeth et al., Next generation sequencing for molecular diagnosis of neurological disorders using ataxias as a model., 2013).

An overview for the hereditary ataxias can be found elsewhere (Bird, Hereditary Ataxia Overview, 1998).

Molecular Medicine Laboratory, Concord Repatriation General Hospital

Website: http://www.slhd.nsw.gov.au/sswps/crgh/molmedicine/gene_molmed.pdf
Mail: Molecular Medicine Laboratory, Clinical Sciences Building Concord Hospital, NSW 2139, Australia
Phone: +61-2-97677009
Fax: +61-2-97676194
Email: molmed@med.usyd.edu.au
Test types
Repeat expansion testing: SCA1, 2, 3, 4, 6, 7, 12, 17
Repeat expansion testing: Friedreich's Ataxia

Oxford Molecular Genetics Laboratory

Website: http://www.ouh.nhs.uk/services/referrals/genetics/genetics-laboratories/molecular-genetics-laboratory/services-by-disorder/documents/InheritedAtaxiasNGS-98gene.pdf
Mail: Genetics Laboratories, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE
Phone: 01865 225594
Fax: 01865 226006
Email: oxford.dnalab@nhs.net
Test type
Next generation sequencing panel: AAAS, AARS, ABCB7, ABHD12, ADCK3, AFG3L2, AMPD2, ANO10, AP1S2, APTX, ARSA, ATCAY, ATP1A3, ATP8A2, C10orf2, CACNA1A, CACNB4, CASK, CCDC88C, CHMP1A, CLN6, CLP1, COX20, CYP27A1 CYP2U1, DARS2, DDHD2, DNMT1, ELOVL5, EXOSC3, FGF14, FLVCR1, FOLR1, GBA2, GOSR2, GRID2, GRM1, HEXA, HEXB, ITPR1, KCNA1, KCNC3, KCND3, KCNJ10, KIAA0226, MRE11A, MTPAP, NPC1, NPC2, OPHN1, PCLO, PDYN, PEX16, PIK3R5, PLA2G6, PMPCA, PNKP, PNPLA6, POLG, PRKCG, PRRT2, RARS2, RNF170, SACS, SEPSECS, SETX, SIL1, SLC1A3, SLC2A1, SLC9A6, SNX14, SPG7, SPTBN2, SRD5A3, STUB1, SYNE1, SYT14, TDP1, TGM6, TMEM240, TPP1, TSEN2, TSEN34, TSEN54, TTBK2, TTC19, TUBB4A, UBR4, UCHL1, VAMP1, VLDLR, VPS53, VRK1, WDR81, WFS1, WWOX, ZFYVE26, ZNF592

Centogene

Website: https://www.centogene.com/genetic-testing/genetic-test-methods/next-generation-sequencing.html
Mail: CENTOGENE AG Schillingallee 68 18057 Rostock, Germany
Phone: +49 (0)381 203 652- 222
Fax: +49 (0)381 203 652-119
Email: dmqc@centogene.com
Test types
SCA NGS panel: ABCB7, ABHD12, ABHD5, ACADVL, ADCK3, AFG3L2, ANO10, APTX, ATCAY, ATM, ATP2B3, C10orf2, CA8, CACNA1A, CCDC88C, CWF19L1, DNMT1, EEF2, ELOVL4, ELOVL5, FGF14, FXN, GRID2, GRM1, ITPR1, KCNC3, KCND3, PDYN, PRKCG, RUBCN, SACS, SETX, SIL1, SLC1A3, SPTBN2, STUB1, SYNE1, SYT14, TDP1, TGM6, TPP1, TTBK2, TTPA, VAMP1, WWOX, ZNF592
Cerebellar ataxia NGS panel: ADCK3, APTX, COQ2, COQ9, DNMT1, FXN, PDSS1, PDSS2, POLG, SACS, SETX, SYNE1, TTPA, VLDLR
Whole exome sequencing
Whole genome sequencing

Genome.One

Website: https://www.genome.one/
Mail: Genome.One
370 Victoria St
Darlinghurst, NSW 2010
Sydney, Australia
Phone: +61 2 9359 8002
Fax: +61 2 9359 8033
Email: clinical@genome.one
Test type
Clinical Whole Genome Sequencing