Childhood onset hereditary spastic paraplegia
Gene: RTN2
Comment on mode of inheritance: As there are sufficient number of cases with biallelic variants and lower limb spasticity, the MOI should be updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' in the next GMS update.Created: 16 Apr 2024, 10:50 p.m. | Last Modified: 16 Apr 2024, 10:50 p.m.
Panel Version: 4.42
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, 10:44 p.m. | Last Modified: 16 Apr 2024, 10:44 p.m.
Panel Version: 4.39
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
distal hereditary motor neuropathy, MONDO:0018894; Lower limb spasticity, HP:0002061
Publications
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, 3:50 p.m. | Last Modified: 28 Mar 2024, 3:50 p.m.
Panel Version: 4.39
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Weakness in the distal upper and lower limbs; Lower limb spasticity; Hyperreflexia
Publications
Adult and childhood onset.Created: 10 May 2019, 9:16 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications
Variants in this GENE are reported as part of current diagnostic practice
Rating and review submitted on behalf of James Polke (Neurogenetics Laboratory,Institute of Neurology, London), on behalf of London North GLH for GMS Neurology specialist test group.Created: 9 May 2019, 4:54 p.m.
In current HSP panel and In Sheffields HSP panelCreated: 28 Apr 2019, 4:16 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Spastic paraplegia 12, autosomal dominant, 604805
Onset of SPG12 usually in the first decadeCreated: 14 Jan 2019, 5:22 p.m.
Onset of SPG12 usually in the first decadeCreated: 14 Jan 2019, 5:22 p.m.
Mode of inheritance for gene: RTN2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant, 604805 to Spastic paraplegia 12, autosomal dominant, OMIM:604805; distal hereditary motor neuropathy, MONDO:0018894; Lower limb spasticity, HP:0002061
Publications for gene: RTN2 were set to 22232211; 24123792; 28362824
Tag Q2_24_MOI tag was added to gene: RTN2. Tag Q2_24_NHS_review tag was added to gene: RTN2.
Publications for gene: RTN2 were set to 22232211
Source Yorkshire and North East GLH was added to RTN2.
Source NHS GMS was added to RTN2.
Source London North GLH was added to RTN2.
Added phenotypes Spastic paraplegia 12, autosomal dominant, 604805 for gene: RTN2
Arianna Tucci: Onset of SPG12 usually in the
Publications for gene: RTN2 were set to Montenegro et al. (2012)
Phenotypes for gene: RTN2 were changed from Spastic paraplegia 12, autosomal dominant to Spastic paraplegia 12, autosomal dominant, 604805
gene: RTN2 was added gene: RTN2 was added to Hereditary spastic paraplegia - childhood onset. Sources: Radboud University Medical Center, Nijmegen,Expert list,Expert Review Green,Illumina TruGenome Clinical Sequencing Services Mode of inheritance for gene: RTN2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: RTN2 were set to Montenegro et al. (2012) Phenotypes for gene: RTN2 were set to Spastic paraplegia 12, autosomal dominant