Motor Neurone Disease

Gene: REEP1

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Spinal muscular atrophy, distal, autosomal recessive, 6, MIM#620011

Green List (high evidence)

HSP – LOF, missense/NMD PTCs
Distal neuropathy/CMT – toxic GOF, stop-loss protein elongations/inframe 5 exon deletion

- Stop-loss variants resulting in an elongated protein result in self-aggregation -> toxic GOF (Bock, 2017)

3’ UTR variants have been reported (OMIM)

Maroofian (2019): 1 hom patient w/ severe congenital distal SMA with diaphragmatic paralysis. Carrier parents "healthy" - not neurologically examined. Same variant reported for AD HSP
Scholottmann (2015): 1 hom patient w/ congenital axonal neuropathy and diaphragmatic palsy. Carrier parents are almost completely normal, fully investigated

Created: 10 Feb 2021, 11:46 p.m. | Last Modified: 10 Feb 2021, 11:46 p.m.

Panel Version: 0.64

Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal

Phenotypes
?Neuronopathy, distal hereditary motor, type VB MIM#614751; Spastic paraplegia 31, autosomal dominant MIM#610250; Charcot-Marie-Tooth; severe congenital distal SMA with diaphragmatic paralysis; congenital axonal neuropathy and diaphragmatic palsy

Publications

• PMID: 27066569
• 31872057
• 22703882
• 29124833

Mode of pathogenicity
Other

Green List (high evidence)

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

Created: 19 Jun 2020, 5:44 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Spastic paraplegia 31, autosomal dominant MIM#610250

Publications

• 23108492
• 22703882