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| Leukodystrophy - adult onset v0.105 | C1R | Zornitza Stark Marked gene: C1R as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Leukodystrophy - adult onset v0.105 | C1R | Zornitza Stark Gene: c1r has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Leukodystrophy - adult onset v0.105 | C1R | Zornitza Stark Classified gene: C1R as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Leukodystrophy - adult onset v0.105 | C1R | Zornitza Stark Gene: c1r has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Leukodystrophy - adult onset v0.104 | C1R |
Deepak Subramanian gene: C1R was added gene: C1R was added to Leukodystrophy - adult onset. Sources: Literature,Other Mode of inheritance for gene: C1R was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: C1R were set to 8958339; 30535813 Phenotypes for gene: C1R were set to Ehlers-Danlos syndrome, periodontal type, 1 (MIM# 130080); Leukodystrophy - adult onset Penetrance for gene: C1R were set to unknown Mode of pathogenicity for gene: C1R was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: C1R was set to AMBER Added comment: Classic periodontal EDS (pEDS) phenotype is associated with gain-of-function mutations in this gene (Kapferer-Seebacher, van Dijk, and Zschocke, GeneReviews, 2021). Earlier case reports noted the presence of leukodystrophy in one 37-year-old female with clinically-diagnosed pEDS (PMID: 8958339) and eight adult individuals from two families with heterozygous mutations in C1R (PMID: 30535813), where other causes of leukodystrophy were ruled out or considered unlikely. Recent data presented at the 2022 EDS International Scientific Symposium by Angwin et al (Oral Abstract 91) highlighted nine more adults with clinically and molecularly confirmed pEDS with evidence of leukodystrophy (out of ten such patients with available imaging). Nearly all patients reported to date have no cognitive deficits or other neurological features of leukodystrophy, with only isolated cases of recurrent headaches/drop attacks or mild cognitive decline/ataxia that might have a different aetiology. Pathophysiology is thought to result from underlying small vessel disease (similar in pattern to that of CADASIL) which progresses with age and is disproportionate to the observed neurological phenotype in these individuals. Sources: Literature, Other |
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