Hereditary spastic paraplegia (Version 1.311)

Description

Hereditary spastic paraplegia inclusion criteria (29490)
- Unexplained spastic paraplegia progressing over >2 years +/-, peripheral neuropathy, or ataxia.
Individuals with syndromic disease or disease onset <30 years should be recruited according to standard guidance, typically as trios. Disease status of apparently unaffected participants should be determined according to standard clinical practice to detect cryptic disease.
In other cases, unaffected individuals should not be recruited. Recruitment in such families should favour multiplex families over single isolated cases. These singleton recruits will not contribute to the overall singleton monitoring metrics applied to GMCs.

Hereditary spastic paraplegia exclusion criteria (29490)
- No structural or inflammatory (MS-like) lesions on brain MRI.

Prior genetic testing guidance (29490)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition.
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Hereditary spastic paraplegia prior genetic testing genes (29490)
Testing of the following genes should be carried out PRIOR TO RECRUITMENT where this is in line with current local practice:
- SPAST, ATL1
- Normal very long chain fatty acid studies

Closing statement (29490)
These requirements will be kept under continual review during the main programme and may be subject to change

Panel Activity

24 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
helen kingston (CMFT NHS Foundation Trust, Manchester)

Group: Other NHS organisation
Workplace: NHS clinical service
Arianna Tucci (Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square)

Group: Other
Workplace: Other
Richard Scott (Genomics England Curator)

Group: Other
Workplace: Other
emma baple (Genomics England Curator)

Group: NHS Genomic Medicine Centre
Workplace: NHS clinical service
Ellen Thomas (Genomics England Curator)

Group: Other
Workplace: Other
Sarah Leigh (Genomics England Curator)

Group: Other
Workplace: Other
Cristina Dias (The Francis Crick Institute)

Group: NHS Genomic Medicine Centre
Workplace: Other
Rebecca Foulger (Genomics England curator)

Group: Other
Workplace: Other
Alice Gardham (Genomics England)

Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)

Group: Other
Workplace: Other
Arianna Tucci (Genomics England Curator)

Group: Other
Workplace: Other
Helen Brittain (Genomics England Curator)

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

Group: Other
Workplace: Other
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
Alistair Pagnamenta (University of Oxford)

Group: GeCIP domain
Workplace: Research lab
Dmitrijs Rots (Children's Clinical University Hospital)

Group: Other
Workplace: Research lab
Catherine Snow (Genomics England)

Group: Other
Workplace: Other
Zerin Hyder (Genomics England)

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

Group: Other
Workplace: Other
Nour Elkhateeb (Cambridge University Hospitals NHS Foundation Trust)

Group: NHS Genomic Medicine Centre
Workplace: NHS clinical service
Achchuthan Shanmugasundram (Genomics England Curator)

Group: Other
Workplace: Other

125 Entities

124 reviewed, 79 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 125 Entitiess
Green Green List (high evidence)	ABCD1	3 reviews 1 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 Literature Phenotypes Hereditary spastic paraplegia adrenal failure VLCFA accumulation spastic paraparesis Adrenoleukodystrophy, 300100 Tags
Green Green List (high evidence)	ABHD16A	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Spastic paraplegia Intellectual disability Tags
Green Green List (high evidence)	ADAR	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Phenotypes Aicardi-Goutieres syndrome 6, OMIM:615010 Tags
Green Green List (high evidence)	AFG3L2	1 review 1 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic ataxia 5, autosomal recessive OMIM:614487 spastic ataxia 5 MONDO:0013776 Spinocerebellar ataxia 28 OMIM:610246 spinocerebellar ataxia type 28 MONDO:0012450 Tags
Green Green List (high evidence)	AIMP1	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Leukodystrophy, hypomyelinating, 3, OMIM:260600 Tags
Green Green List (high evidence)	ALDH18A1	1 review	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Literature Other Phenotypes Spastic paraplegia 9A, autosomal dominant Spastic paraplegia 9B, autosomal recessive CUTIS LAXA, AUTOSOMAL DOMINANT 3 ADCL3 AUTOSOMAL RECESSIVE MENTAL RETARDATION-JOINT HYPERMOBILITY-SKIN LAXITY WITH OR WITHOUT METABOLIC ABNORMALITIES (MRJHSL) SPASTIC PARAPLEGIA 9, AUTOSOMAL DOMINANT SPG9 Tags
Green Green List (high evidence)	ALS2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Amyotrophic lateral sclerosis 2, juvenile, OMIM:205100 Primary lateral sclerosis, juvenile, OMIM:606353 Spastic paralysis, infantile onset ascending, OMIM:607225 Tags
Green Green List (high evidence)	AP4B1	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 47, autosomal recessive, OMIM:614066 Hereditary spastic paraplegia 47, MONDO:0013551 Tags
Green Green List (high evidence)	AP4E1	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 51, autosomal recessive, OMIM:613744 Hereditary spastic paraplegia 51, MONDO:0013401 Tags
Green Green List (high evidence)	AP4M1	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 50, autosomal recessive Tags
Green Green List (high evidence)	AP4S1	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 52, autosomal recessive developmental delay seizures Tags
Green Green List (high evidence)	ARG1	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Argininemia, OMIM:207800 Tags
Green Green List (high evidence)	ATL1	3 reviews 3 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Eligibility statement prior genetic testing Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 3A, autosomal dominant, Spastic Paraplegia, Dominant Spastic paraplegia 3A, autosomal dominant Tags
Green Green List (high evidence)	ATP13A2	3 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes 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	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS 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 Review Expert Review Green NHS GMS Phenotypes Spinocerebellar ataxia 1, OMIM:164400 Tags STR
Green Green List (high evidence)	ATXN2_CAG STR	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS 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	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Machado-Joseph disease, OMIM:109150 Tags STR
Green Green List (high evidence)	ATXN7_CAG STR	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Spinocerebellar ataxia 7, OMIM:164500 Tags STR
Green Green List (high evidence)	B4GALNT1	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 26, autosomal recessive Tags
Green Green List (high evidence)	BSCL2	2 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Silver spastic paraplegia syndrome, OMIM:270685 Tags
Green Green List (high evidence)	C12orf65	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 55, autosomal recessive, OMIM:615035 Tags new-gene-name
Green Green List (high evidence)	C19orf12	3 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert list Expert Review Green 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	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Spinocerebellar ataxia 6, OMIM:183086 Tags STR
Green Green List (high evidence)	CAPN1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Spastic paraplegia 76 autosomal recessive 616907 Tags
Green Green List (high evidence)	CYP27A1	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Cerebrotendinous xanthomatosis, 213700 progressive lower extremity spasticity,often disproportionate to any degree of weakness Tags
Green Green List (high evidence)	CYP2U1	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 56, autosomal recessive Tags
Green Green List (high evidence)	CYP7B1	4 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 5A, autosomal recessive , OMIM:270800 Tags
Green Green List (high evidence)	DDHD1	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 28, autosomal recessive Tags
Green Green List (high evidence)	DDHD2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 54, autosomal recessive Tags
Green Green List (high evidence)	ENTPD1	2 reviews 1 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 64, autosomal recessive, OMIM:615683 Tags
Green Green List (high evidence)	ERLIN1	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Other Phenotypes Hereditary spastic paraplegia Spastic paraplegia 62, 615681 Tags
Green Green List (high evidence)	ERLIN2	1 review	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 18, autosomal recessive, 611225 Spastic paraplegia, autosomal dominant hereditary spastic paraplegia neurodegeneration Tags
Green Green List (high evidence)	FA2H	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 35, autosomal recessive Tags
Green Green List (high evidence)	FARS2	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Spastic paraplegia 77, autosomal recessive, 617046 Tags
Green Green List (high evidence)	FXN_GAA STR	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green NHS GMS Phenotypes Friedreich ataxia, OMIM:229300 Friedreich ataxia with retained reflexes, OMIM:229300 Tags STR
Green Green List (high evidence)	GBA2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 46, autosomal recessive, 614409 Tags
Green Green List (high evidence)	HACE1	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Spastic paraplegia psychomotor retardation seizure Spastic paraplegia and psychomotor retardation with or without seizures, 616756 Tags
Green Green List (high evidence)	HIKESHI	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Leukodystrophy, hypomyelinating, 13, OMIM:616881 Tags
Green Green List (high evidence)	HSPD1	4 reviews 2 green	BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Leukodystrophy, hypomyelinating, 4, OMIM:612233 (AR) Spastic paraplegia 13, autosomal dominant, OMIM:605280 (AD) Tags
Green Green List (high evidence)	HTT_CAG STR	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Huntington disease, OMIM:143100 Tags STR
Green Green List (high evidence)	KDM5C	5 reviews 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 Green Literature Phenotypes Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type, OMIM:300534 Tags
Green Green List (high evidence)	KIDINS220	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Other Phenotypes Spastic paraplegia, intellectual disability, nystagmus, and obesity OMIM:617296 Tags
Green Green List (high evidence)	KIF1A	5 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen 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	5 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic ataxia 2, autosomal recessive, OMIM:611302 Tags
Green Green List (high evidence)	KIF5A	4 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 10, autosomal dominant Tags
Green Green List (high evidence)	L1CAM	1 review 1 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert list Expert Review Green UKGTN 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
Green Green List (high evidence)	MAG	4 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Spastic paraplegia 75, autosomal recessive, OMIM:616680 Tags
Green Green List (high evidence)	NIPA1	4 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 6, autosomal dominant Spasticparaplegia6,autosomaldominant,600363 Tags
Green Green List (high evidence)	NKX6-2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy, OMIM:617560 Tags
Green Green List (high evidence)	NT5C2	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 45, autosomal recessive, 613162 Tags
Green Green List (high evidence)	OPA3	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Other Phenotypes 3-methylglutaconic aciduria, type III, 258501 Costeff syndrome Tags
Green Green List (high evidence)	PCYT2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Complex hereditary spastic paraplegia 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 list Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 2, X-linked Tags
Green Green List (high evidence)	PNPLA6	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 39, autosomal recessive Tags
Green Green List (high evidence)	POLR3A	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Autosomal Recessive Ataxia Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism Tags
Green Green List (high evidence)	PPP2R2B_CAG STR	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Spinocerebellar ataxia 12, OMIM:604326 Tags STR
Green Green List (high evidence)	REEP1	4 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 31, autosomal dominant Tags
Green Green List (high evidence)	REEP2	3 reviews	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert Review Green Literature Other Phenotypes ?Spastic paraplegia 72, autosomal recessive, 615625 ?Spastic paraplegia 72, autosomal dominant,615625 Tags
Green Green List (high evidence)	RNASEH2B	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Other Phenotypes Aicardi-Goutieres syndrome 2, OMIM:610181 Tags
Green Green List (high evidence)	RTN2	4 reviews 2 green	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 12, autosomal dominant, OMIM:604805 distal hereditary motor neuropathy, MONDO:0018894 Lower limb spasticity, HP:0002061 Tags
Green Green List (high evidence)	SACS	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic ataxia, Charlevoix-Saguenay type Tags
Green Green List (high evidence)	SERAC1	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Other Phenotypes 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, OMIM:614739 Tags
Green Green List (high evidence)	SLC16A2	1 review 1 green	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert list Expert Review Green Phenotypes Allan-Herndon-Dudley syndrome, OMIM:300523 Tags
Green Green List (high evidence)	SLC1A4	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Expert Review Green Phenotypes Spastic tetraplegia, thin corpus callosum, and progressive microcephaly, 616657 Tags
Green Green List (high evidence)	SLC25A46	2 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Neuropathy, hereditary motor and sensory, type VIB 616505 Tags
Green Green List (high evidence)	SLC2A1	3 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature Phenotypes Developmental delay seizure paroxysmal choreoathetosis spastic paraplegia autosomal dominant, complicated hereditary spastic paraplegia (HSP) Tags
Green Green List (high evidence)	SPART	3 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green UKGTN Phenotypes Troyer syndrome, OMIM:275900 Spastic paraplegia 20 Tags
Green Green List (high evidence)	SPAST	3 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Eligibility statement prior genetic testing Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 4, autosomal dominant, OMIM:182601 hereditary spastic paraplegia 4, MONDO:0008438 Tags
Green Green List (high evidence)	SPG11	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 11, autosomal recessive Tags
Green Green List (high evidence)	SPG21	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services UKGTN Phenotypes Spastic Paraplegia, 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 list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 7, autosomal recessive, OMIM:607259 hereditary spastic paraplegia 7, MONDO:0011803 Tags
Green Green List (high evidence)	TBP_CAG STR	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green NHS GMS Phenotypes Spinocerebellar ataxia 17, OMIM:607136 Tags STR
Green Green List (high evidence)	TFG	4 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Spastic paraplegia 57, autosomal recessive, OMIM:615658 Tags
Green Green List (high evidence)	TUBB4A	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Expert Review Green Phenotypes Dystonia 4, torsion, autosomal dominant 128101 Leukodystrophy, hypomyelinating, 6 612438 ataxia Tags
Green Green List (high evidence)	UBAP1	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature Phenotypes Hereditary spastic paraplegia Tags
Green Green List (high evidence)	WASHC5	5 reviews 2 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 8, autosomal dominant, OMIM:603563 Tags
Green Green List (high evidence)	WDR45B	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Literature Phenotypes Neurodevelopmental disorder with spastic quadriplegia and brain abnormalities with or without seizures, OMIM:617977 Tags
Green Green List (high evidence)	ZFYVE26	2 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 15, autosomal recessive Tags
Amber Amber List (moderate evidence)	CDK16	2 reviews	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Amber Literature Phenotypes Intellectual disability and spastic paraplegia Tags
Amber Amber List (moderate evidence)	DARS	4 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Brain stem and spinal cord Hypomyelination leg spasticity Hypomyelination with brainstem and spinal cord involvement and leg spasticity, 615281 Tags new-gene-name
Amber Amber List (moderate evidence)	GCH1	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Amber Literature Phenotypes Dystonia Spastic paraplegia progressive spastic paraplegia Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230 Tags
Amber Amber List (moderate evidence)	IBA57	3 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes ?Spastic paraplegia 74, autosomal recessive, OMIM:616451 Tags
Amber Amber List (moderate evidence)	LYST	4 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes spastic paraplegia Chediak-Higashi syndrome, 214500 Tags
Amber Amber List (moderate evidence)	MARS2	3 reviews 2 green	Not set	Sources Expert Review Amber Radboud University Medical Center, Nijmegen Phenotypes Spastic ataxia 3, autosomal recessive Tags cnv gene-duplication
Amber Amber List (moderate evidence)	MTPAP	3 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Radboud University Medical Center, Nijmegen UKGTN Phenotypes Ataxia, spastic, 4 Spastic ataxia 4, autosomal recessive Tags
Amber Amber List (moderate evidence)	POLR3K	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Leukodystrophy, hypomyelinating, 21, OMIM:619310 Tags founder-effect watchlist
Amber Amber List (moderate evidence)	SARS2	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Literature Phenotypes Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis 613845 Progressive Spastic Paresis Tags
Amber Amber List (moderate evidence)	SLC33A1	4 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Amber Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 42, autosomal dominant, Tags
Red Red List (low evidence)	AMPD2	3 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Phenotypes Pontocerebellar hypolplasia (biallelic) Hereditary Spastic Paraplegia? Tags
Red Red List (low evidence)	AP5Z1	3 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 48, autosomal recessive, OMIM:613647 Tags
Red Red List (low evidence)	ARL6IP1	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Tags
Red Red List (low evidence)	ARSI	1 review 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Tags
Red Red List (low evidence)	CCT5	1 review 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Neuropathy, hereditary sensory, with spastic paraplegia Sensory Neuropathy with Spastic Paraplegia Tags
Red Red List (low evidence)	DSTYK	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Other Phenotypes Spastic paraplegia 23, 270750 Tags founder-effect
Red Red List (low evidence)	GAD1	1 review 1 red	Not set	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Cerebralpalsy,spasticquadriplegic,1,603513 Tags
Red Red List (low evidence)	GJC2	4 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Radboud University Medical Center, Nijmegen UKGTN Phenotypes Spastic paraplegia 44, autosomal recessive Tags
Red Red List (low evidence)	KLC4	3 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Literature Phenotypes spastic paraplegia progressive complicated spastic paraplegia Tags
Red Red List (low evidence)	MARS	3 reviews 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Tags new-gene-name
Red Red List (low evidence)	PCDH12	2 reviews 2 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Phenotypes intellectual disability microcephaly epilepsy perithalamic hyperechogenicity periventricular hyperechogenicity midbrain abnormalities hypothalamic abnormalities Tags founder-effect
Red Red List (low evidence)	PGAP1	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Tags
Red Red List (low evidence)	PSEN1	3 reviews 1 green	Not set	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Alzheimer disease, type 3, with spastic paraparesis and apraxia Alzheimer disease, type 3, with spastic paraparesis and unusual plaques Tags
Red Red List (low evidence)	RAB3GAP2	3 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Literature Phenotypes Martsolf syndrome 1, OMIM:212720 Warburg micro syndrome 2, OMIM:614225 Tags
Red Red List (low evidence)	TECPR2	4 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 49, autosomal recessive, 615031 Tags
Red Red List (low evidence)	USP8	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Tags
Red Red List (low evidence)	VAMP1	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Spastic ataxia 1, autosomal dominant, 108600 Tags founder-effect
Red Red List (low evidence)	VPS37A	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 53, autosomal recessive Tags
Red Red List (low evidence)	WDR48	2 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Red Tags
Red Red List (low evidence)	ZEB2	2 reviews 2 red	Not set	Sources Expert Review Red UKGTN Tags
Red Red List (low evidence)	ZFYVE27	2 reviews 1 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Spastic paraplegia 33, autosomal dominant Tags
No list No list	EIF2B5	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Phenotypes progressive cerebellar ataxia spasticity cognitive impairment Tags
No list No list	SPG14	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG16	3 reviews	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG19	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG23	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG24	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG25	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG27	3 reviews 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG29	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG32	3 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG34	3 reviews	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG36	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG37	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG38	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only
No list No list	SPG41	3 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Removed Tags curated_removed ensembl_ids_known_missing locus-type-phenotype-only

Major version comments

12.05.16 - Reviews were internally assessed, and panel was revised and promoted to Version 1.

Hereditary spastic paraplegia (Version 1.311)

24 reviewers

125 Entities

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