Adult onset leukodystrophy

Gene: OCRL

I don't know

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

Created: 4 May 2024, 5:32 p.m. | Last Modified: 4 May 2024, 5:44 p.m.

Panel Version: 4.3

I don't know

As Lowe syndrome (OMIM:309000) is present at birth, it may be inappropriate to have OCRL as a green gene on this panel - Adult onset leukodystrophy. In a clinical review of Lowe syndrome, PMID: 16722554 notes that congenital bilateral cataract is present at the birth in all patients, further symptoms have a variable occurrence.

Created: 12 Oct 2023, 4:06 p.m. | Last Modified: 12 Oct 2023, 4:06 p.m.

Panel Version: 3.21

Publications

• 16722554

Genotype/Phenotype information: PMID: 33517444 - Ramadesikan et al 2021 - studied the cellular effect of 7 OCRL1 (OCRL) variants identified in Lowe Syndrome patients in kidney epithelial cells. Differences in cell spreading, ciliogenesis, protein localization and degree of Golgi apparatus fragmentation were observed. The results help provide a framework to explains symptom heterogeneity and may help stratify patients.

Created: 4 May 2021, 5:02 p.m. | Last Modified: 4 May 2021, 5:02 p.m.

Panel Version: 1.8

Publications

• 33517444

Red List (low evidence)

Typically onset in infancy/childhood.

Created: 21 Jun 2020, 6:35 a.m. | Last Modified: 21 Jun 2020, 6:35 a.m.

Panel Version: 1.4

Phenotypes
Lowe syndrome, MIM# 309000

Green List (high evidence)

I don't know

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

Phenotypes
Lowe syndrome, 309000

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