Adult onset leukodystrophy

Gene: AARS

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://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142409/ - classical adult onset leukodystrophy, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880494/ - well defined large Swedish family with HDLS/ALSP, https://pubmed.ncbi.nlm.nih.gov/35911843/ (this is a child with reversible white matter lesions but supports idea that white matter changes are part of the AARS spectrum)

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

Panel Version: 4.3

Added the Q4_21_rating tag to make it clear that the rating of this gene is being assessed.

Created: 6 Oct 2022, 1:48 p.m. | Last Modified: 6 Oct 2022, 1:48 p.m.

Panel Version: 1.47

Comment on publications: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142409/ is PMID: 37106376. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880494/ is PMID: 31775912

Created: 30 Jul 2024, 12:36 p.m. | Last Modified: 30 Jul 2024, 12:36 p.m.

Panel Version: 4.4

As the recommendation is to demote AARS from Green to Amber on this panel, the to_be_confirmed_NHSE tag has been added, as further NHSE review is required.

Created: 15 Mar 2022, 6:05 p.m. | Last Modified: 15 Mar 2022, 6:05 p.m.

Panel Version: 1.40

I don't know

AARS2 has well established link to leukodystrophy, can only find limited evidence for AARS.

Created: 21 Jun 2020, 6:09 a.m. | Last Modified: 21 Jun 2020, 6:09 a.m.

Panel Version: 1.4

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Charcot-Marie-Tooth disease, axonal, type 2N 613287

Publications

• 31775912

Green List (high evidence)

I don't know

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Charcot-Marie-Tooth disease, axonal, type 2N, 613287

I don't know

Added new-gene-name tag, new approved HGNC gene symbol for AARS is AARS1

Created: 6 Sep 2019, 11:54 a.m. | Last Modified: 6 Sep 2019, 11:54 a.m.

Panel Version: 0.15

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