Adult onset leukodystrophy

Gene: RPS6KA3

Red List (low evidence)

The rating of this gene has been updated to red following NHS Genomic Medicine Service approval.

Created: 4 May 2024, 5:32 p.m. | Last Modified: 4 May 2024, 5:42 p.m.

Panel Version: 4.3

Red List (low evidence)

Comment on list classification: There is not enough evidence for this gene to be rated GREEN at the next major review.

Created: 8 Aug 2023, 12:39 p.m. | Last Modified: 8 Aug 2023, 12:39 p.m.

Panel Version: 3.10

RPS6KA3 is associated with Coffin-Lowry syndrome (OMIM:303600) OMIM and as definitive Gen2Phen gene for the same condition. Although over 19 different RPS6KA3 variants have been reported in Coffin-Lowry syndrome patients, only one has been associated with abnormalities in white matter, in three siblings (PMID: 16691578).

Created: 8 Aug 2023, 12:38 p.m. | Last Modified: 8 Aug 2023, 12:38 p.m.

Panel Version: 3.9

Publications

• 16691578

Red List (low evidence)

One family reported with white matter changes, which does not appear to be a prominent feature of the condition.

Created: 21 Jun 2020, 6:41 a.m. | Last Modified: 21 Jun 2020, 6:41 a.m.

Panel Version: 1.4

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Coffin-Lowry syndrome MIM#303600

Publications

• 16691578

Green List (high evidence)

I don't know

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Coffin-Lowry syndrome, 303600

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