Amyotrophic lateral sclerosis/motor neuron disease

Gene: SPG11

Green List (high evidence)

There is know phenotypic overlap between the axonopathies ALS, SPG and CMT so pleiotropy here is not surprising - there is good evidence of association with juvenile ALS. GM2-gangliosidosis has also been seen in a patient with SPG11 mutations, indicating a wide phenotypic spectrum and complex phenotypes.

"Spastic paraplegia 11 (SPG11) is the most prevalent form of autosomal recessive hereditary spastic paraplegia, resulting from biallelic pathogenic variants in the SPG11 gene (OMIM 610844)."

"SPG11 pathogenic variants are also associated with a spectrum of clinical manifestations, including juvenile amyotrophic lateral sclerosis (ALS), hereditary motor sensory neuropathy (Charcot–Marie–Tooth disease type 2X), and multiple sclerosis mimics" Stevanin G. Spastic Paraplegia 11 Seattle (WA): University of Washington Available from: https://www.ncbi.nlm.nih.gov/books/NBK1210/?report=classic

see also OMIM: Amyotrophic lateral sclerosis 5, juvenile 602099 (AR); Charcot-Marie-Tooth disease, axonal, type 2X 616668 (AR); Spastic paraplegia 11, autosomal recessive 604360 (AR).

Created: 2 Jul 2024, 1:02 p.m. | Last Modified: 2 Jul 2024, 1:02 p.m.

Panel Version: 1.69

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Juvenile amyotrophic lateral sclerosis (ALS) with long survival; hereditary motor sensory neuropathy (Charcot–Marie–Tooth disease type 2X), and multiple sclerosis

Publications

• PubMed: 20110243
• PMID: 36445564
• PMID: 37133535
• PMID: 27066562
• PMID: 25681989
• PMID: 38938072

I don't know

The gene is included in other panels (e.g., spastic paraplegia), but one of the phenotypes could be also ALS
Sources: Literature

Created: 17 Jun 2021, 11:02 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Amyotrophic lateral sclerosis 5, juvenile

Publications

• https://doi.org/10.1093/brain/awp325