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

15 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: Genomics England

  • 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

  • Chris Buxton (North Bristol NHS Trust)

    Group: NHS Genomic Medicine Centre
    Workplace: NHS diagnostic lab

  • Alistair Pagnamenta (University of Oxford)

    Group: GeCIP domain
    Workplace: Research lab

119 Entities

118 reviewed, 69 green

List Entity Reviews Mode of inheritance Details
119 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)
ADAR
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Aicardi-Goutieres syndrome 6, 615010
Tags
Green Green List (high evidence)
AFG3L2
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Ataxia, spastic, 5, autosomal recessive
  • Spastic ataxia 5, autosomal recessive
Tags
Green Green List (high evidence)
AIMP1
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Green
Phenotypes
  • 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
  • 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
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
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
  • Argininaemia, 207800
  • Progressive spastic tetraplegia
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
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Spinocerebellar ataxia 10 603516
Tags
  • STR
Green Green List (high evidence)
ATXN1_CAG
STR
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Spinocerebellar ataxia 1 164400
Tags
  • STR
Green Green List (high evidence)
ATXN2_CAG
STR
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Spinocerebellar ataxia 2 183090
Tags
  • STR
Green Green List (high evidence)
ATXN3_CAG
STR
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Machado-Joseph disease 109150
Tags
  • STR
Green Green List (high evidence)
ATXN7_CAG
STR
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Spinocerebellar ataxia 7 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,
Tags
Green Green List (high evidence)
C12orf65
2 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Spasticparaplegia55,autosomalrecessive,615035
Tags
Green Green List (high evidence)
C19orf12
2 reviews
2 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Green
Tags
Green Green List (high evidence)
CACNA1A_CAG
STR
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Spinocerebellar ataxia 6 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
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)
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
1 review
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Friedreich ataxia 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)
HSPD1
3 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 13, autosomal dominant
Tags
Green Green List (high evidence)
HTT_CAG
STR
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Huntington disease 143100
Tags
  • STR
Green Green List (high evidence)
KIDINS220
1 review
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Other
Phenotypes
  • Spastic paraplegia, intellectual disability, nystagmus, and obesity 617296
Tags
Green Green List (high evidence)
KIF1A
3 reviews
2 green
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 recessive
Tags
  • watchlist
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
  • X-linked hydrocephalus, MASA syndrome, Hereditary spastic paraplegia
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 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)
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
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Spinocerebellar ataxia 12 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)
RTN2
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert list
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Spastic paraplegia 12, autosomal dominant
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, 614739
  • MEGDEL syndrome
  • 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome
  • MEGDHEL syndrome
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
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
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
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
3 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 7, autosomal recessive
Tags
Green Green List (high evidence)
TBP_CAG
STR
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review
  • Expert Review Green
Phenotypes
  • Spinocerebellar ataxia 17 607136
Tags
  • STR
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
Tags
Green Green List (high evidence)
WDR45B
1 review
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Literature
Phenotypes
  • profound developmental delay, early-onset refractory epilepsy, progressive spastic quadriplegia and contractures, and brain malformations.
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, 616451
Tags
Amber Amber List (moderate evidence)
KDM5C
4 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 Amber
  • Literature
Phenotypes
  • Mental retardation, X-linked, syndromic, Claes-Jensen type, 300534
  • Intellectual disability
  • developmental delay
  • progressive spasticity
  • epilepsy
  • hypothyroidism
Tags
  • watchlist
Amber Amber List (moderate evidence)
KIF1C
4 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Amber
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Spastic ataxia 2,autosomal recessive
Tags
  • watchlist
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)
MAG
3 reviews
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
Phenotypes
  • Spastic paraplegia 75, autosomal recessive, 616680
Tags
  • watchlist
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)
REEP2
2 reviews
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
  • Literature
  • Other
Phenotypes
  • ?Spastic paraplegia 72, autosomal recessive, 615625
  • ?Spastic paraplegia 72, autosomal dominant,615625
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
Amber Amber List (moderate evidence)
TFG
3 reviews
1 green
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Amber
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, Recessive
  • Spastic paraplegia 48, autosomal recessive
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)
ENTPD1
1 review
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Red
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Spasticparaplegia64,615683
Tags
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
  • spastic paraplegia
  • Warburg micro syndrome 2, 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
  • 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
  • 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
  • locus-type-phenotype-only
No list No list
SPG23
3 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Removed
Tags
  • locus-type-phenotype-only
No list No list
SPG24
3 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Removed
Tags
  • locus-type-phenotype-only
No list No list
SPG25
3 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Removed
Tags
  • locus-type-phenotype-only
No list No list
SPG27
3 reviews
1 red
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Removed
Tags
  • locus-type-phenotype-only
No list No list
SPG29
3 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Removed
Tags
  • locus-type-phenotype-only
No list No list
SPG32
3 reviews
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert list
  • Expert Review Removed
Tags
  • 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
  • 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
  • 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
  • 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
  • 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
  • locus-type-phenotype-only

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