Adult onset leukodystrophy

Gene: COL4A2

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/pmid/35699195/ - reviewed all published cases (n=41), 29% had white matter hyperintensities; https://link.springer.com/article/10.1007/s00415-016-8280-3 - 17y, diffuse leukocencephalopathy; https://pubmed.ncbi.nlm.nih.gov/24390199/ - 29y, diffuse leukocencephalopathy

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 so it is clear it is the rating of this gene that is being assessed.

Created: 6 Oct 2022, 2:08 p.m. | Last Modified: 6 Oct 2022, 2:08 p.m.

Panel Version: 1.47

Comment on publications: https://link.springer.com/article/10.1007/s00415-016-8280-3 is PMID: 27624120

Created: 30 Jul 2024, 12:47 p.m. | Last Modified: 30 Jul 2024, 12:47 p.m.

Panel Version: 4.5

As the recommendation is to demote COL4A2 from Green to Red on this panel, the to_be_confirmed_NHSE tag has been added, as further NHSE review is required.

Created: 15 Mar 2022, 6:06 p.m. | Last Modified: 15 Mar 2022, 6:06 p.m.

Panel Version: 1.40

Red List (low evidence)

Cannot find specific reports linking variants in this gene with leukodystrophy (unlike the association between COL4A1 and leukodystrophy). Brain abnormalities described typically include porencephaly, schizencephaly, polymicrogyria, pachygyria, and subcortical and subependymal nodular heterotopia.

Created: 21 Jun 2020, 6:15 a.m. | Last Modified: 21 Jun 2020, 6:15 a.m.

Panel Version: 1.4

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Brain small vessel disease 2, MIM# 614483

Green List (high evidence)

I don't know

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

Phenotypes
Brain small vessel disease 2, 614483

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