Adult onset hereditary spastic paraplegia (Version 3.21)

The latest signed off version for the GMS is v3.14. The current version, shown here, may differ from the signed-off version.

Description

This panel is used for clinical indication 'R60 Adult onset hereditary spastic paraplegia' in the NHS Genomic Medicine Service.

Further information on the testing criteria and any overlapping clinical indications can be found within (https://www.england.nhs.uk/publication/national-genomic-test-directories/) under 'R60 Adult onset hereditary spastic paraplegia'.

A version of this panel has been signed off under NHS Genomic Medicine Service governance (see 'Latest signed off version' in the panel header information).

This panel will continue to be curated based on external reviews and Genomics England curation. New changes will be reflected in an increase to the minor version of the panel and details of these can be viewed in the 'Panel Activity' page. Periodically, these changes will be reviewed by a NHS Genomic Medicine Service evaluation process. The content that is agreed for the GMS panels will be reflected in an updated signed off version number.

CNVs, STRs and genes encoded by the mitochondrial genome may not be routinely included in the analysis where the panel is NOT delivered by WGS. Please contact your Genomic Laboratory Hub for information regarding specific queries.

Some of the genes in this panel cause conditions that typically present in adulthood. Please consider this when applying the panel.

Panel Activity

16 reviewers

Sarah Leigh (Genomics England Curator)

Group: Other
Workplace: Other
Rebecca Foulger (Genomics England curator)

Group: Other
Workplace: Other
James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Group: GeCIP domain
Workplace: NHS diagnostic lab
Louise Daugherty (Genomics England Curator)

Group: Other
Workplace: Other
Eleanor Williams (Genomics England Curator)

Group: Other
Workplace: Other
Michael Bonello (The Walton Centre NHS Foundation Trust)

Group: GeCIP domain
Workplace: NHS clinical service
Zornitza Stark (Australian Genomics)

Group: Other
Workplace: Other clinical service
Chris Buxton (North Bristol NHS Trust)

Group: NHS Genomic Medicine Centre
Workplace: NHS diagnostic lab
Ivone Leong (Genomics England Curator)

Group: Other
Workplace: Other
Julia Baptista (Royal Devon and Exeter NHS Foundation Trust)

Group: Other NHS organisation
Workplace: NHS diagnostic lab
Nick Beauchamp (Sheffield Diagnostic Genetics Service)

Group: GeCIP domain
Workplace: NHS diagnostic lab
Catherine Snow (Genomics England)

Group: Other
Workplace: Other
Arina Puzriakova (Genomics England Curator)

Group: Other
Workplace: Other
James Polke (North Thames GLH)

Group: Other NHS organisation
Workplace: NHS diagnostic lab
Mafalda Gomes (Genomics England Curator)

Group: Other
Workplace: Other
Achchuthan Shanmugasundram (Genomics England Curator)

Group: Other
Workplace: Other

117 Entities

117 reviewed, 63 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 117 Entitiess
Green Green List (high evidence)	ABCD1	3 reviews 2 green	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes spastic paraparesis Hereditary spastic paraplegia adrenal failure VLCFA accumulation Adrenoleukodystrophy, 300100 Tags
Green Green List (high evidence)	ADAR	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Aicardi-Goutieres syndrome 6, OMIM:615010 Tags
Green Green List (high evidence)	ALDH18A1	3 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 9B, autosomal recessive 616586 SPG9 ADCL3 AUTOSOMAL RECESSIVE MENTAL RETARDATION-JOINT HYPERMOBILITY-SKIN LAXITY WITH OR WITHOUT METABOLIC ABNORMALITIES (MRJHSL) SPASTIC PARAPLEGIA 9, AUTOSOMAL DOMINANT Cutis laxa, autosomal dominant 3 616603 Spastic paraplegia 9A, autosomal dominant 601162 Cutis laxa, autosomal recessive, type IIIA 219150 Tags
Green Green List (high evidence)	AP4B1	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 47, autosomal recessive, OMIM:614066 Hereditary spastic paraplegia 47, MONDO:0013551 Tags for-review to_be_confirmed_NHSE
Green Green List (high evidence)	AP4E1	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 51, autosomal recessive, OMIM:613744 Hereditary spastic paraplegia 51, MONDO:0013401 Tags for-review to_be_confirmed_NHSE
Green Green List (high evidence)	AP4M1	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 50, autosomal recessive, 612936 Tags for-review to_be_confirmed_NHSE
Green Green List (high evidence)	AP4S1	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes developmental delay seizures Spastic paraplegia 52, autosomal recessive, 614067 Tags for-review to_be_confirmed_NHSE
Green Green List (high evidence)	AP5Z1	4 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic Paraplegia, Recessive Spastic paraplegia 48, autosomal recessive, 613647 Spastic paraplegia 48, autosomal recessive Tags
Green Green List (high evidence)	ATL1	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 3A, 182600 autosomal dominant Spastic Paraplegia, Dominant Neuropathy, hereditary sensory, type ID, 613708 Tags
Green Green List (high evidence)	ATP13A2	4 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Kufor-Rakeb syndrome, 606693 AR Adult-onset lower-limb predominant spastic paraparesis Spastic paraplegia 78, autosomal recessive, 617225 complicated hereditary spastic paraplegia Tags
Green Green List (high evidence)	ATXN10_ATTCT STR	5 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green London North GLH NHS GMS South West GLH Phenotypes Spinocerebellar ataxia 10, OMIM:603516 Tags STR
Green Green List (high evidence)	ATXN1_CAG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green London North GLH NHS GMS South West GLH Phenotypes Spinocerebellar ataxia 1, OMIM:164400 Tags STR
Green Green List (high evidence)	ATXN2_CAG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green London North GLH NHS GMS South West GLH Phenotypes Spinocerebellar ataxia 2, OMIM:183090 {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090 Tags STR
Green Green List (high evidence)	ATXN3_CAG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green London North GLH NHS GMS South West GLH Phenotypes Machado-Joseph disease, OMIM:109150 Tags STR
Green Green List (high evidence)	ATXN7_CAG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green London North GLH NHS GMS South West GLH Phenotypes Spinocerebellar ataxia 7, OMIM:164500 Tags STR
Green Green List (high evidence)	B4GALNT1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 26, autosomal recessive, 609195 Tags
Green Green List (high evidence)	BSCL2	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Silver spastic paraplegia syndrome, OMIM:270685 Neuropathy, distal hereditary motor, type VC, OMIM:619112 Tags
Green Green List (high evidence)	C19orf12	5 reviews 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes ?Spastic paraplegia 43, autosomal recessive, OMIM:615043 Neurodegeneration with brain iron accumulation 4, OMIM: 614298 Tags
Green Green List (high evidence)	CACNA1A_CAG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green London North GLH NHS GMS South West GLH Phenotypes Spinocerebellar ataxia 6, OMIM:183086 Tags STR
Green Green List (high evidence)	CAPN1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 76 autosomal recessive, 616907 Tags
Green Green List (high evidence)	COQ4	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature NHS GMS Phenotypes Coenzyme Q10 deficiency, primary, 7, OMIM:616276 Tags
Green Green List (high evidence)	CPT1C	5 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 73, autosomal dominant, OMIM:616282 Tags
Green Green List (high evidence)	CYP27A1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Cerebrotendinous xanthomatosis, 213700 progressive lower extremity spasticity,often disproportionate to any degree of weakness Tags
Green Green List (high evidence)	CYP7B1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 5A, autosomal recessive, 270800 Tags
Green Green List (high evidence)	DARS	4 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes leg spasticity Brain stem and spinal cord Hypomyelination Hypomyelination with brainstem and spinal cord involvement and leg spasticity, 615281 Tags new-gene-name
Green Green List (high evidence)	DDHD1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 28, autosomal recessive, 609340 Tags
Green Green List (high evidence)	DDHD2	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 54, autosomal recessive, 615033 Tags
Green Green List (high evidence)	ERLIN2	3 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia, autosomal dominant neurodegeneration. Spastic paraplegia 18, autosomal recessive, 611225 hereditary spastic paraplegia Tags
Green Green List (high evidence)	FA2H	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 35, autosomal recessive, 611026 Tags
Green Green List (high evidence)	FBXO7	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Parkinson disease 15, autosomal recessive, OMIM:260300 Tags
Green Green List (high evidence)	FXN	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Phenotypes Friedreich ataxia OMIM:229300 Friedreich ataxia with retained reflexes OMIM:229300 Friedreich ataxia 1 MONDO:0100340 Tags nucleotide-repeat-expansion
Green Green List (high evidence)	FXN_GAA STR	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green London North GLH NHS GMS South West GLH Phenotypes Friedreich ataxia, OMIM:229300 Friedreich ataxia with retained reflexes, OMIM:229300 Tags STR
Green Green List (high evidence)	GALC	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Krabbe disease, OMIM:245200 Tags
Green Green List (high evidence)	GBA2	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 46, autosomal recessive, 614409 Tags
Green Green List (high evidence)	GBE1	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Polyglucosan body disease, adult form, OMIM:263570 Tags
Green Green List (high evidence)	GCH1	5 reviews 3 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS North West GLH South West GLH Yorkshire and North East GLH Phenotypes Dystonia progressive spastic paraplegia Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230 Spastic paraplegia Tags
Green Green List (high evidence)	GJA1	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green Phenotypes Oculodentodigital dysplasia, OMIM:164200 Spastic paraplegia Tags
Green Green List (high evidence)	KCNA2	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Hereditary spastic paraplegia and ataxia Tags
Green Green List (high evidence)	KIF1A	3 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 30, autosomal dominant, OMIM:610357 Spastic paraplegia 30, autosomal recessive, OMIM:610357 NESCAV syndrome, OMIM:614255 Tags
Green Green List (high evidence)	KIF1C	6 reviews 3 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic ataxia 2, autosomal recessive, 611302 Spastic ataxia 2, autosomal recessive Tags
Green Green List (high evidence)	KIF5A	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 10, autosomal dominant or pseudoautosomal, NOT imprinted, 604187 Tags
Green Green List (high evidence)	NIPA1	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spasticparaplegia 6,autosomal dominant, pseudoautosomal, NOT imprinted, 600363 Tags
Green Green List (high evidence)	OPA3	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes 3-methylglutaconic aciduria, type III, 258501 Costeff syndrome, Optic atrophy 3 with cataract, 165300, AD Tags
Green Green List (high evidence)	PCYT2	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Spastic paraplegia 82, autosomal recessive, 618770 Tags
Green Green List (high evidence)	PLP1	3 reviews 2 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 2, X-linked recessive, 312920 Tags
Green Green List (high evidence)	PNPLA6	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 39, autosomal recessive, 612020 Tags
Green Green List (high evidence)	POLR3A	3 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism, 607694 Autosomal Recessive Ataxia Tags
Green Green List (high evidence)	PPP2R2B_CAG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green London North GLH NHS GMS South West GLH Phenotypes Spinocerebellar ataxia 12, OMIM:604326 Tags STR
Green Green List (high evidence)	PSEN1	4 reviews 2 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Alzheimer disease, type 3, with spastic paraparesis, apraxia and unusual plaques Alzheimer disease, type 3, with spastic paraparesis and apraxia Alzheimer disease, type 3, with spastic paraparesis and unusual plaques Tags
Green Green List (high evidence)	REEP1	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 31, autosomal dominant, 610250 Tags
Green Green List (high evidence)	RTN2	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 12, autosomal dominant, 604805 Tags
Green Green List (high evidence)	SACS	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic ataxia, Charlevoix-Saguenay type, 270550 Tags
Green Green List (high evidence)	SLC25A15	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome, OMIM:238970 Tags
Green Green List (high evidence)	SPAST	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 4, autosomal dominant, OMIM:182601 hereditary spastic paraplegia 4, MONDO:0008438 Tags
Green Green List (high evidence)	SPG11	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 11, autosomal recessive, 604360 Charcot-Marie-Tooth disease, axonal, type 2X, 616668, AR Amyotrophic lateral sclerosis 5, juvenile, 602099, AR Tags
Green Green List (high evidence)	SPG21	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Mast syndrome, 248900 Spastic Paraplegia, autosomal recessive Tags
Green Green List (high evidence)	SPG7	4 reviews 2 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 7, autosomal recessive, OMIM:607259 hereditary spastic paraplegia 7, MONDO:0011803 Tags Q2_23_MOI
Green Green List (high evidence)	SPTAN1	2 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Literature NHS GMS Phenotypes Developmental and epileptic encephalopathy 5, OMIM:613477 developmental and epileptic encephalopathy, 5, MONDO:0013277 Tags
Green Green List (high evidence)	TBP_CAG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Green London North GLH NHS GMS South West GLH Phenotypes Spinocerebellar ataxia 17, OMIM:607136 Tags STR
Green Green List (high evidence)	TUBB4A	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Dystonia 4, torsion, autosomal dominant, 128101 ataxia Leukodystrophy, hypomyelinating, 612438 AD Tags
Green Green List (high evidence)	UBAP1	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Hereditary spastic paraplegia Tags
Green Green List (high evidence)	WASHC5	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 8, autosomal dominant, OMIM:603563 Tags
Green Green List (high evidence)	ZFYVE26	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 15, autosomal recessive, 270700 Tags
Amber Amber List (moderate evidence)	AFG3L2	5 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic ataxia 5, autosomal recessive, OMIM:614487 Tags
Amber Amber List (moderate evidence)	AIMP1	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Leukodystrophy, hypomyelinating, 3, OMIM:260600 Tags
Amber Amber List (moderate evidence)	ALS2	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Amyotrophic lateral sclerosis 2, juvenile, OMIM:205100 Primary lateral sclerosis, juvenile, OMIM:606353 Tags
Amber Amber List (moderate evidence)	AMPD2	4 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes ?Spastic paraplegia 63, 615686, AR Hereditary Spastic Paraplegia? Pontocerebellar hypoplasia, type 9, 615809, AR Pontocerebellar hypolplasia (biallelic) Tags
Amber Amber List (moderate evidence)	ARG1	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Progressive spastic tetraplegia Argininaemia, 207800 Tags
Amber Amber List (moderate evidence)	ARL6IP1	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic paraplegia 61, autosomal recessive, 615685 Tags
Amber Amber List (moderate evidence)	C12orf65	7 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 55, autosomal recessive, OMIM:615035 Tags new-gene-name
Amber Amber List (moderate evidence)	CHP1	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Spastic ataxia 9, autosomal recessive, OMIM:618438 Tags watchlist
Amber Amber List (moderate evidence)	CYP2U1	5 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 56, autosomal recessive OMIM:615030 hereditary spastic paraplegia 56 MONDO:0014015 Tags
Amber Amber List (moderate evidence)	DSTYK	4 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic paraplegia 23, 270750, AR Spastic paraplegia 23, 270750 Congenital anomalies of kidney and urinary tract 1, 610805, AD Tags
Amber Amber List (moderate evidence)	ENTPD1	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic paraplegia 64, autosomal recessive, OMIM:615683 Tags
Amber Amber List (moderate evidence)	ERLIN1	7 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Hereditary spastic paraplegia Spastic paraplegia 62, 615681 Tags
Amber Amber List (moderate evidence)	FARS2	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 77, autosomal recessive, 617046 Tags
Amber Amber List (moderate evidence)	GAD1	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Cerebralpalsy, spasticquadriplegic,1, 603513 Tags
Amber Amber List (moderate evidence)	GJC2	4 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic paraplegia 44, autosomal recessive Spastic paraplegia 44, autosomal recessive 613206, AR Leukodystrophy, hypomyelinating, 2, 608804, AR Tags
Amber Amber List (moderate evidence)	HACE1	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes seizure Spastic paraplegia and psychomotor retardation with or without seizures, 616756 psychomotor retardation Spastic paraplegia Tags
Amber Amber List (moderate evidence)	HSPD1	5 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 13, autosomal dominant, OMIM:605280 Tags
Amber Amber List (moderate evidence)	IBA57	4 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes ?Spastic paraplegia 74, autosomal recessive, OMIM:616451 Tags
Amber Amber List (moderate evidence)	KDM5C	7 reviews 2 green 1 red	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type, OMIM:300534 Tags
Amber Amber List (moderate evidence)	KIDINS220	6 reviews 1 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia, intellectual disability, nystagmus, and obesity, OMIM:617296 Tags
Amber Amber List (moderate evidence)	L1CAM	6 reviews 1 green 1 red	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes CRASH syndrome, OMIM:303350 MASA syndrome, OMIM:303350 Hydrocephalus due to aqueductal stenosis, OMIM:307000 Hydrocephalus with congential idiopathic intestinal pseudoobstruction, OMIM:307000 Hydrocephalus with Hirschsprung disease, OMIM:307000 Tags
Amber Amber List (moderate evidence)	LYST	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes spastic paraplegia Chediak-Higashi syndrome, 214500 Spastic paraplegia Tags
Amber Amber List (moderate evidence)	MARS2	4 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic ataxia 3, autosomal recessive, 611390 Spastic ataxia 3, autosomal recessive Tags
Amber Amber List (moderate evidence)	MTPAP	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Ataxia, spastic, 4 ?Spastic ataxia 4, autosomal recessive, 613672 Spastic ataxia 4, autosomal recessive Tags
Amber Amber List (moderate evidence)	NKX6-2	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, 617560 Tags
Amber Amber List (moderate evidence)	NT5C2	7 reviews 2 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic paraplegia 45, autosomal recessive, 613162 Tags
Amber Amber List (moderate evidence)	PRNP	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Amber NHS GMS Phenotypes Gerstmann-Straussler disease, OMIM: 137440 Gerstmann-Straussler-Scheinker syndrome, MONDO:0007656 Tags Q3_23_promote_green
Amber Amber List (moderate evidence)	RAB3GAP2	4 reviews 1 green 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Martsolf syndrome 1, OMIM:212720 Warburg micro syndrome 2, OMIM:614225 Tags
Amber Amber List (moderate evidence)	REEP2	7 reviews 2 green 1 red	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes ?Spastic paraplegia 72, autosomal dominant, 615625 ?Spastic paraplegia 72, autosomal dominant,615625 ?Spastic paraplegia 72, autosomal recessive, 615625 Tags
Amber Amber List (moderate evidence)	SERAC1	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, OMIM:614739 Tags
Amber Amber List (moderate evidence)	SLC16A2	6 reviews 1 green 1 red	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Allan-Herndon-Dudley syndrome, OMIM:300523 Tags
Amber Amber List (moderate evidence)	SLC1A4	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, OMIM:616657 Tags
Amber Amber List (moderate evidence)	SPART	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Troyer syndrome, OMIM:275900 Spastic paraplegia 20 Tags
Amber Amber List (moderate evidence)	TECPR2	4 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic paraplegia 49, autosomal recessive, 615031 Spastic paraplegia 49, autosomal recessive,615031, AR Tags
Amber Amber List (moderate evidence)	TFG	7 reviews 3 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic paraplegia 57, autosomal recessive, OMIM:615658 Tags
Amber Amber List (moderate evidence)	UCHL1	6 reviews 2 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Spastic paraplegia 79B, autosomal recessive, OMIM:615491 early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome, MONDO:0014209 Spastic paraplegia 79A, autosomal dominant, OMIM:620221 Tags Q3_23_MOI Q3_23_promote_green
Amber Amber List (moderate evidence)	VAMP1	4 reviews 1 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic ataxia 1, autosomal dominant, 108600 Tags
Amber Amber List (moderate evidence)	VPS37A	4 reviews 1 green 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic paraplegia 53, autosomal recessive Spastic paraplegia 53, autosomal recessive, 614898, AR Tags
Amber Amber List (moderate evidence)	WDR45B	6 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, OMIM:617977 Tags
Amber Amber List (moderate evidence)	WDR48	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic paraplegia Tags
Red Red List (low evidence)	ARSI	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources NHS GMS South West GLH Yorkshire and North East GLH Tags
Red Red List (low evidence)	CCT5	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Sensory Neuropathy with Spastic Paraplegia Neuropathy, hereditary sensory, with spastic paraplegia Tags
Red Red List (low evidence)	CDK16	3 reviews 2 red	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Red London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Intellectual disability and spastic paraplegia, x-linked Tags
Red Red List (low evidence)	KLC4	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources NHS GMS South West GLH Yorkshire and North East GLH Phenotypes spastic paraplegia progressive complicated spastic paraplegia Tags
Red Red List (low evidence)	MAG	5 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic paraplegia 75, autosomal recessive, OMIM:616680 Tags
Red Red List (low evidence)	MARS	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources NHS GMS South West GLH Yorkshire and North East GLH Tags new-gene-name
Red Red List (low evidence)	PCDH12	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources NHS GMS South West GLH Yorkshire and North East GLH Phenotypes microcephaly perithalamic hyperechogenicity midbrain abnormalities intellectual disability epilepsy periventricular hyperechogenicity hypothalamic abnormalities Tags
Red Red List (low evidence)	PGAP1	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources NHS GMS South West GLH Yorkshire and North East GLH Tags
Red Red List (low evidence)	SLC25A46	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red London North GLH NHS GMS Yorkshire and North East GLH Phenotypes Neuropathy, hereditary motor and sensory, type VIB, 616505 Tags
Red Red List (low evidence)	SLC33A1	4 reviews 1 green 2 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red London North GLH NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Congenital cataracts, hearing loss, and neurodegeneration 614482, AR:Spastic paraplegia 42, autosomal dominant, 612539 AD Spastic paraplegia 42, autosomal dominant Tags
Red Red List (low evidence)	USP8	3 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources NHS GMS South West GLH Yorkshire and North East GLH Tags
Red Red List (low evidence)	ZEB2	3 reviews 2 red	Not set	Sources NHS GMS South West GLH Yorkshire and North East GLH Tags
Red Red List (low evidence)	ZFYVE27	3 reviews 2 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources NHS GMS South West GLH Yorkshire and North East GLH Phenotypes Spastic paraplegia 33, autosomal dominant Tags
No list No list	HTT_CAG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert list Expert Review Removed London North GLH NHS GMS South West GLH Phenotypes Huntington disease, OMIM:143100 Tags curated_removed STR

Major version comments

2023-03-22 15:54 Catherine Snow (Genomics England) promoted panel to 3.0
The content of this panel has been updated in accordance with changes agreed with the NHS Genomic Medicine Service. The panel was promoted to the next major version (3.0) following this.

2022-11-30 14:32 Eleanor Williams (Genomics England Curator) promoted panel to 2.0
The content of this panel has been updated in accordance with changes agreed with the NHS Genomic Medicine Service. The panel was promoted to the next major version (2.0) following this.

2019-10-18 14:52 Louise Daugherty (Genomics England Curator) promoted panel to 1.0
The content of this panel (version 0.156) was signed off under NHS Genomic Medicine Service governance on (18/10/2019). The panel was promoted to the next major version (version 1.0) as a result of this.

Adult onset hereditary spastic paraplegia (Version 3.21)

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