Hereditary ataxia with onset in adulthood
Gene: COQ4
The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 10 Oct 2023, 4:24 p.m. | Last Modified: 10 Oct 2023, 4:29 p.m.
Panel Version: 4.24
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Comment on classification of this gene: The rating for this gene should be added as GREEN, as this gene has been implicated in adult-onset ataxia, as identified from biallelic variants from three unrelated individuals/ families.
Six patients from four families with bi-allelic variants were reported with adult-Onset ataxia-spasticity spectrum phenotype. Out of these, five patients from three families with bi-allelic variants (c.305G>A & c.473G>A, c.434G>A & c.437T>G, c.202+4A>C & c.202+4A>C) were identified with gait and/or limb ataxia. The severity of the phenotype ranged from mild (c.305G>A & c.473G>A) to more severe (c.202+4A>C & c.202+4A>C ) and the age of onset ranged from 15 to 34 (PMID:36047608).
COQ4 was not associated with adult-onset ataxia-spasticity spectrum disease in OMIM or Gene2Phenotype. However, functional studies performed in patient-derived fibroblasts, yeasts and zebrafish larvae confirms the role of COQ4 in brain development. The coq4 F0 CRISPR zebrafish line particularly showed motor defects and cell reduction in a specific area of the hindbrain, a region reminiscent of the human cerebellum (PMID:33704555).
Sources: LiteratureCreated: 10 Dec 2022, 9:12 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Coenzyme Q10 deficiency, primary, 7, OMIM:616276
Publications
Tag Q4_22_promote_green was removed from gene: COQ4.
Source NHS GMS was added to COQ4. Source Expert Review Green was added to COQ4. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: COQ4 were changed from Adult-onset ataxia-spasticity spectrum disease; Hereditary spastic paraparesis, MONDO:0019064; Cerebellar ataxia, MONDO:0000437 to Coenzyme Q10 deficiency, primary, 7, OMIM:616276
Tag Q4_22_promote_green tag was added to gene: COQ4.
Gene: coq4 has been classified as Amber List (Moderate Evidence).
gene: COQ4 was added gene: COQ4 was added to Hereditary ataxia - adult onset. Sources: Literature Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: COQ4 were set to 36047608 Phenotypes for gene: COQ4 were set to Adult-onset ataxia-spasticity spectrum disease; Hereditary spastic paraparesis, MONDO:0019064; Cerebellar ataxia, MONDO:0000437 Review for gene: COQ4 was set to GREEN