MDSANZ: Not-for-profit membership organisation

open to medical personnel who have a clinical or research interest in movement disorders

Genetic Testing for Inherited Movement Disorders

 

SUGGESTIONS FOR 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

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).

 

Options:


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

 

 

Hereditary ataxia

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).

 

Options:


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


 

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