Motor Neurone Disease

Gene: ATL1

Green List (high evidence)

Neuropathy: Autosomal dominant hereditary sensory neuropathy type 1D is characterized by adult onset of a distal axonal sensory neuropathy affecting all modalities, often associated with distal ulceration and amputation as well as hyporeflexia, although some patients may show features suggesting upper neuron involvement. Five unrelated families reported.

HSP: both mono-allelic and bi-allelic disease, with bi-allelic being earlier onset and more severe. Hom nonsense (PMID: 24473461) and hom missense (PMID: 26888483) were reported for AR HSP. Disease mechanism (PTC variants): LoF. Disease mechanism (missense variants): Dominant negative: Mutant atlastin-1 protein functionally impair the atlastin-1 oligomer by binding to WT protein —> reduce GTPase activity (PMID: 16537571) —> cause HSP3A.

Variants fall outside of the GTPase related motifs or the conserved motifs are linked to neuropathy, suggesting an alternative mechanism is used apart from dom-neg (PMID: 28396731) —> cause HSN1D

More than 90% of the mutations were located in exon 4, 7, 8 and 12 (PMID: 16401858)

Created: 30 Apr 2021, 9:38 p.m. | Last Modified: 30 Apr 2021, 9:38 p.m.

Panel Version: 0.7447

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Neuropathy, hereditary sensory, type ID , MIM#613708; MONDO:0013381; Spastic paraplegia 3A, MIM 182600; Hereditary spastic paraplegia, AR

Publications

• 21194679
• 24604904
• 22340599
• 16401858
• 16537571
• 17657515
• 28396731
• 24473461
• 26888483

Green List (high evidence)

The HSP caused by this gene can be classified as a non-ALS MND, affecting the upper motor neurons.
Sources: Expert list

Created: 19 Jun 2020, 3:41 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Spastic paraplegia 3A, autosomal dominant MIM#182600

Publications

• 16765570