Adult onset leukodystrophy
Gene: RNF216After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains green. Additional evidence supplied from David Lynch, lead for HSS adult onset Leukodystrophy service: https://pubmed.ncbi.nlm.nih.gov/25841028/ - 2 unrelated families, adult onset, extensive white matter lesions; https://pubmed.ncbi.nlm.nih.gov/38050071/ - literature review of 17 families, average age of onset 29y, white matter lesions in 96%Created: 4 May 2024, 5:32 p.m. | Last Modified: 4 May 2024, 5:32 p.m.
Panel Version: 4.3
Comment on list classification: There is not enough evidence for this gene to be rated GREEN on this panel at the next major review.Created: 8 Aug 2023, 2:05 p.m. | Last Modified: 8 Aug 2023, 2:05 p.m.
Panel Version: 3.13
RNF216 variants are associated with Cerebellar ataxia and hypogonadotropic hypogonadism (OMIM:212840), previously known as Gordon Holmes syndrome (GDHS). No phenotype was associated with RNF216 in Gen2Phen.
At least six variants have been reported in four unrelated cases of OMIM:212840. Three of these variants, in four individuals from two unrelated families, have been associated with a variant of GDHS. The variant GDHS includes Huntingtons-like features including white matter lesions (PMID: 25841028).Created: 8 Aug 2023, 1:30 p.m. | Last Modified: 8 Aug 2023, 1:39 p.m.
Panel Version: 3.12
Publications
Can only find two unrelated cases reported with white matter changes.Created: 21 Jun 2020, 6:39 a.m. | Last Modified: 21 Jun 2020, 6:39 a.m.
Panel Version: 1.4
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Cerebellar ataxia and hypogonadotropic hypogonadism MIM#212840
Publications
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Cerebellar ataxia and hypogonadotropic hypogonadism, 212840
Review and rating uploaded from file (Consensus gene list for R62 Adult-Onset Leukodystrophy - Leeds.xlsx) submitted by Ian Berry (Leeds Genetics Laboratory) on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group. Phenotype and MOI not submitted.Created: 4 Jul 2019, 4:32 p.m. | Last Modified: 4 Jul 2019, 4:32 p.m.
Panel Version: 0.10
Included all genes listed in clinical cases in Lynch et al 2015 PMID:28334938 and Ayrignac et al. 2015 PMID: 25527826. Included all genes with clear adult onset listed in Vanderver 2017 PMID:27159321 and Ahmed et al. 2017 PMID:24357685. A small number of genes from these resources were omitted, particularly those with limited or single case reports referenced in Ahmed et al, those with a metabolic basis (that could be determined by standard metabolic assays), and recessive diseases where the likelihood of encountering incidental carrier status is far more likely than finding a diagnosis e.g. Cockayne syndrome. Due to variable expressivity and potential later onset of phenotype in hypomorphic cases, peroxisomal biogenesis disorders OMIM phenotypic Series PS214100 and GeneReviews PMID:20301621 included.Created: 4 Jul 2019, 4:06 p.m. | Last Modified: 4 Jul 2019, 4:06 p.m.
Panel Version: 0.9
Publications
Variants in this GENE are reported as part of current diagnostic practice
Tag Q3_23_expert_review was removed from gene: RNF216. Tag Q3_23_demote_amber was removed from gene: RNF216.
Tag Q3_23_expert_review tag was added to gene: RNF216.
Gene: rnf216 has been classified as Green List (High Evidence).
Tag Q3_23_demote_amber tag was added to gene: RNF216.
Phenotypes for gene: RNF216 were changed from Cerebellar ataxia and hypogonadotropic hypogonadism, 212840 to Cerebellar ataxia and hypogonadotropic hypogonadism, OMIM:212840
Publications for gene: RNF216 were set to 27159321; 25527826; 28334938; 20301621; 24357685
Mode of inheritance for gene RNF216 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes Cerebellar ataxia and hypogonadotropic hypogonadism, 212840 for gene: RNF216
Publications for gene RNF216 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Source Expert Review Green was added to RNF216. Rating Changed from Red List (low evidence) to Green List (high evidence)
Source NHS GMS was added to RNF216.
gene: RNF216 was added gene: RNF216 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH Mode of inheritance for gene: RNF216 was set to