White matter disorders and cerebral calcification - narrow panelGene: FIG4
The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.
Created: 14 Mar 2022, 2 p.m. | Last Modified: 14 Mar 2022, 2 p.m.
Panel Version: 1.224
Comment on list classification: Promoting from grey to amber, but with a recommendation for green rating at the next GMS review as there are 4 cases with variants in this gene and a leukoencephalopathy phenotype, plus a supportive mouse model.
Created: 29 Apr 2021, 10:19 p.m. | Last Modified: 29 Apr 2021, 10:19 p.m.
Panel Version: 1.58
As reported by expert reviewer 4 families reported together with a supportive mouse model.
PMID: 30740813 - Lenk et al 2019 - report 4 unrelated families with leukoencephalopathy in which biallelic FIG4 variants were found, inherited from heterozygous parents. Variants were identified by exome sequencing or WGS. Disease onset was in early childhood. A range of phenotypes were recorded including skeletal (1 family) and macular (1 family) features, and variable degrees of CNS myelination. Functional studies with cultured fibroblasts showed enlarged vacuoles indicating FIG4 dysfunction.
PMID: 29688489 - Mironova et al 2018 - using inducible knock-out of Fig4 mice they shows that neonatal knockout of Fig4 results in massive spongiform degeneration in neocortical layers IV and V and thinning of myelinated fibers in the corpus callosum and white matter in cerebellar lobules. Knock out of Fig4 in adult mice shows Fig4 is required for white matter repair.
Created: 29 Apr 2021, 10:15 p.m. | Last Modified: 29 Apr 2021, 10:15 p.m.
Panel Version: 1.56
Four unrelated families reported with bi-allelic variants in this gene and a leukoencephalopathy phenotype. Mouse model recapitulates the phenotype. Please note gene is associated with multiple other phenotypes including Yunis-Varon syndrome, CMT, ALS
Sources: Expert list
Created: 15 Sep 2020, 10:31 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Charcot-Marie-Tooth disease, type 4J 611228; Yunis-Varon syndrome 216340; leukoencephalopathy
Variants in this GENE are reported as part of current diagnostic practice
Tag Q2_21_rating was removed from gene: FIG4.
Source Expert Review Green was added to FIG4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: fig4 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: FIG4 were changed from Charcot-Marie-Tooth disease, type 4J 611228; Yunis-Varon syndrome 216340; leukoencephalopathy to Charcot-Marie-Tooth disease, type 4J, OMIM:611228; Yunis-Varon syndrome, OMIM:216340; leukoencephalopathy, HP:0002352
Tag Q2_21_rating tag was added to gene: FIG4.
gene: FIG4 was added gene: FIG4 was added to White matter disorders and cerebral calcification - narrow panel. Sources: Expert list Mode of inheritance for gene: FIG4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FIG4 were set to 30740813; 29688489 Phenotypes for gene: FIG4 were set to Charcot-Marie-Tooth disease, type 4J 611228; Yunis-Varon syndrome 216340; leukoencephalopathy Review for gene: FIG4 was set to GREEN gene: FIG4 was marked as current diagnostic