Motor Neurone Disease

Gene: KIF5A

Green List (high evidence)

Neonatal intractable myoclonus is a severe neurologic disorder characterized by the onset of intractable myoclonic seizures soon after birth. Affected infants have intermittent apnea, abnormal eye movements, pallor of the optic nerve, and lack of developmental progress. Brain imaging shows a progressive leukoencephalopathy. At least 3 unrelated individuals with de novo LoF variants.

SPG10/CMT: variants are generally in the motor domain.

Created: 12 Mar 2022, 1:19 a.m. | Last Modified: 12 Mar 2022, 1:19 a.m.

Panel Version: 0.11286

Mutations in the KIF5A are associated with a wide phenotypic spectrum from hereditary spastic paraplegia (HSP) to axonal Charcot-Marie-Tooth peripheral neuropathy type 2 (CMT2).

Multiple families reported with neuropathy alone as well as HSP in association with neuropathy.

Created: 6 May 2021, 10:45 a.m. | Last Modified: 6 May 2021, 10:45 a.m.

Panel Version: 0.114

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neuropathy; Spastic paraplegia 10, autosomal dominant, MIM# 604187; Myoclonus, intractable, neonatal, MIM# 617235

Publications

• 30057544
• 29892902
• 28902413
• 26403765
• 25695920
• 25008398
• 27463701
• 27414745

Green List (high evidence)

12 patients from 9 unrelated families with ALS, had heterozygous LOF variants in the C-terminal region cargo-binding region. Variants causing SPG10 are almost exclusively missense mutations that affect the N-terminal motor domain.
Sources: Expert list

Created: 31 Mar 2020, 8:24 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
{Amyotrophic lateral sclerosis, susceptibility to, 25} MIM#617921

Publications

• 29342275
• 30301576
• 29566793