Hereditary neuropathy or pain disorder
Gene: RTN2
Comment on list classification: There is sufficient evidence available for the association of RTN2 biallelic variants with distal hereditary motor neuropathy. Hence, this gene should be promoted to green rating in the next GMS update.Created: 16 Apr 2024, 1:47 p.m. | Last Modified: 16 Apr 2024, 1:47 p.m.
Panel Version: 3.89
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. Nerve conduction studies revealed axonal motor neuropathy with neurogenic changes in the electromyography.
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.
Sources: LiteratureCreated: 16 Apr 2024, 1:45 p.m. | Last Modified: 16 Apr 2024, 10:44 p.m.
Panel Version: 3.89
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
distal hereditary motor neuropathy, MONDO:0018894
Publications
Gene: rtn2 has been classified as Amber List (Moderate Evidence).
Tag Q2_24_promote_green tag was added to gene: RTN2.
gene: RTN2 was added gene: RTN2 was added to Hereditary neuropathy or pain disorder. Sources: Literature Mode of inheritance for gene: RTN2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RTN2 were set to 38527963 Phenotypes for gene: RTN2 were set to distal hereditary motor neuropathy, MONDO:0018894 Review for gene: RTN2 was set to GREEN