Hereditary spastic paraplegia

Gene: RTN2

Green List (high evidence)

Comment on mode of inheritance: As there are sufficient number of cases with biallelic variants and lower limb spasticity, the MOI has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal'.

Created: 16 Apr 2024, 11:15 p.m. | Last Modified: 16 Apr 2024, 11:15 p.m.

Panel Version: 1.311

As reviewed by Nour Elkhateeb, PMID:38527963 reported the identification of seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven unrelated families with distal hereditary motor neuropathy. All affected individuals exhibited weakness in the distal upper and lower limbs, lower limb spasticity, hyperreflexia, with an onset in the first decade of life.

Characterisation of C. elegans RTN2 homolog loss-of-function variants demonstrated morphological and behavioural differences compared to the parental strain, and treatment with an endoplasmic/sarcoplasmic reticulum Ca(2+) re-uptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences.

Biallelic variants in RTN2 gene have not yet been associated with any phenotypes in OMIM or Gene2Phenotype, while monoallelic variants have been associated with spastic paraplegia (MIM #604805) in OMIM.

Created: 16 Apr 2024, 11:13 p.m. | Last Modified: 16 Apr 2024, 11:13 p.m.

Panel Version: 1.308

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
distal hereditary motor neuropathy, MONDO:0018894; Lower limb spasticity, HP:0002061

Publications

• 38527963

A recent publication has been described seven novel or ultra-rare homozygous loss-of-function RTN2 variants in 14 individuals from seven consanguineous families with distal hereditary motor neuropathy (dHMN) with pyramidal features.

Created: 28 Mar 2024, 3:21 p.m. | Last Modified: 28 Mar 2024, 3:49 p.m.

Panel Version: 1.308

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Weakness in the distal upper and lower limbs; Lower limb spasticity; Hyperreflexia

Publications

• PMID: 38527963

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)

> 3 unrelated cases plus functional data.
Segregation not completed in sporadic cases.

Created: 7 Feb 2016, 10:22 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Hereditary spastic paraplegia

Publications

• 22232211