Adult onset leukodystrophy

Gene: RNF216

After 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

I don't know

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

• 25841028

I don't know

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

• 28334938
• 26250479

Green List (high evidence)

I don't know

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cerebellar ataxia and hypogonadotropic hypogonadism, 212840

I don't know

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

Green List (high evidence)

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

• 28334938
• 25527826
• 27159321
• 24357685
• 20301621

Variants in this GENE are reported as part of current diagnostic practice