Hereditary spastic paraplegia

Gene: SPAST

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, 4:49 p.m. | Last Modified: 12 Mar 2025, 4:49 p.m.

Panel Version: 1.314

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, 4:32 p.m. | Last Modified: 12 Mar 2025, 4:32 p.m.

Panel Version: 1.312

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

This gene is on the Hereditary Spastic Paraplagia (HSP) NGS Panel in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual.

Created: 14 Jun 2016, 9:37 a.m.

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• 26094131
• 23897027
• 10610178
• 10891911
• 11039577

Green List (high evidence)

By far the most common cause of pure HSP. All types of mutations described.

Created: 13 Jan 2016, 3:18 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
pure hereditary spastic paraplegia

Publications

• 26094131
• 23897027
• 10610178
• 10891911
• 11039577

Mode of pathogenicity
Other