Adult onset leukodystrophy
Gene: RPS6KA3
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
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
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
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 tag was added to gene: RPS6KA3.
Gene: rps6ka3 has been classified as Green List (High Evidence).
Tag Q3_23_demote_red tag was added to gene: RPS6KA3.
Phenotypes for gene: RPS6KA3 were changed from Coffin-Lowry syndrome, 303600 to Coffin-Lowry syndrome, OMIM:303600
Mode of inheritance for gene RPS6KA3 was changed from to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Added phenotypes Coffin-Lowry syndrome, 303600 for gene: RPS6KA3
Publications for gene RPS6KA3 were changed from to 27159321; 25527826; 28334938; 20301621; 24357685
Source Expert Review Green was added to RPS6KA3. Rating Changed from Red List (low evidence) to Green List (high evidence)
Source NHS GMS was added to RPS6KA3.
gene: RPS6KA3 was added gene: RPS6KA3 was added to White matter disorders - adult onset. Sources: Yorkshire and North East GLH Mode of inheritance for gene: RPS6KA3 was set to