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  2. Childhood onset hereditary spastic paraplegia
  3. SPAST

Childhood onset hereditary spastic paraplegia

Gene: SPAST

Green List (high evidence)
SPAST (spastin)
EnsemblGeneIds (GRCh38): ENSG00000021574
EnsemblGeneIds (GRCh37): ENSG00000021574
OMIM: 604277, Gene2Phenotype
SPAST is in 9 panels

5 reviews

Sarah Leigh (Genomics England Curator)

Comment on publications: PMID: 39731306 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.
Created: 12 Mar 2025, 4:46 p.m. | Last Modified: 12 Mar 2025, 4:46 p.m.
Panel Version: 7.8
Numerous heterozygous SPAST variants have been associated with Spastic paraplegia 4, autosomal dominant (OMIM:182601). PMID: 39731306 reports five homozygous SPAST variants in nine individuals from six families with spastic paraplegia and neurodegeneration. Amongst the homozygous children, all had lower limb spasticity, 5/6 had upper limb spasticity and 3/6 had severe intellectual disability. Evidence of consanguinity was evident in five of the families and the parents of the homozygous children were heterozygous for the SPAST variant found in the child, these carrier parents were asymptomatic in all but one the families studied.
Created: 12 Mar 2025, 4:30 p.m. | Last Modified: 12 Mar 2025, 4:30 p.m.
Panel Version: 7.7

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Created: 12 Mar 2025, 4:30 p.m.
Last Modified: 12 Mar 2025, 4:30 p.m.
Panel version: 7.7

Nick Beauchamp (Sheffield Diagnostic Genetics Service)

Green List (high evidence)

Adult and childhood onset.
Created: 10 May 2019, 9:58 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Variants in this GENE are reported as part of current diagnostic practice

Created: 10 May 2019, 9:58 a.m.

Panel version: 1.74

Louise Daugherty (Genomics England Curator)

I don't know

Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.
Created: 9 May 2019, 4:54 p.m.
Created: 28 Apr 2019, 5:14 p.m.

Panel version: 1.74

James Polke (Neurogenetics Laboratory, Institute of Neurology, London)

Green List (high evidence)

In current HSP panel and In Sheffields HSP panel
Created: 28 Apr 2019, 4:16 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Spastic paraplegia 4, autosomal dominant, 182601

Created: 28 Apr 2019, 4:16 p.m.

Panel version: 1.6

Arianna Tucci (Genomics England Curator)

I don't know

Onset is mostly in early adulthood - but it is variable and has been described from infancy through senescence
Created: 25 Feb 2019, 10:59 a.m.
Created: 25 Feb 2019, 10:59 a.m.

Panel version: 1.0

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Yorkshire and North East GLH
  • NHS GMS
  • London North GLH
  • Illumina TruGenome Clinical Sequencing Services
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Expert list
  • Radboud University Medical Center, Nijmegen
  • UKGTN
Phenotypes
  • Spastic paraplegia 4, autosomal dominant, OMIM:182601
  • hereditary spastic paraplegia 4, MONDO:0008438
Tags
Q1_25_ MOI
OMIM
604277
Clinvar variants
Variants in SPAST
Penetrance
None
Publications
Panels with this gene

History Filter Activity

12 Mar 2025, Gel status: 3

Set publications

Sarah Leigh (Genomics England Curator)

Publications for gene: SPAST were set to Hazan et al (1999); 10610178; 10699187; 11039577; 10980739; 15210521; 16832076

12 Mar 2025, Gel status: 3

Added Tag

Sarah Leigh (Genomics England Curator)

Tag Q1_25_ MOI tag was added to gene: SPAST.

14 Mar 2023, Gel status: 3

Set Phenotypes

Sarah Leigh (Genomics England Curator)

Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant, 182601 to Spastic paraplegia 4, autosomal dominant, OMIM:182601; hereditary spastic paraplegia 4, MONDO:0008438

13 May 2019, Gel status: 4

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: SPAST were set to Hazan et al (1999)

13 May 2019, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for gene: SPAST were changed from Spastic paraplegia 4, autosomal dominant to Spastic paraplegia 4, autosomal dominant, 182601

13 May 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Yorkshire and North East GLH was added to SPAST.

28 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to SPAST.

28 Apr 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to SPAST.

3 Apr 2019, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Added phenotypes Spastic paraplegia 4, autosomal dominant for gene: SPAST

28 Jan 2019, Gel status: 4

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

Arianna Tucci: Onset at birth

19 Dec 2018, Gel status: 4

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Sarah Leigh (Genomics England Curator)

gene: SPAST was added gene: SPAST was added to Hereditary spastic paraplegia - childhood onset. Sources: UKGTN,Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green,Eligibility statement prior genetic testing,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: SPAST was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: SPAST were set to Hazan et al (1999) Phenotypes for gene: SPAST were set to Spastic paraplegia 4, autosomal dominant