Cerebral amyloid angiopathy

Gene: ITM2B

Green List (high evidence)

At least 4 unrelated families with dementia as a prominent feature of the phenotype and stop loss or protein elongating variants, and a supporting mouse model. Variants that result in the generation of peptide, which is deposited as amyloid fibrils causing neuronal disfunction and dementia.
PMID: 10391242 - familial British dementia (FBD) stop loss variant (c.799T>A p.Ter267Arg) in British kindred with progressive dementia, spasticity, and cerebellar ataxia, with onset at around the fifth decade of life.
PMID: 10781099 - familial Danish dementia protein elongating variant (c.787_796dup p.Ser266fs) identified in a large Danish kindred with a dominant disorder characterised by cataracts, deafness, progressive ataxia, and dementia.
PMID: 33814452 - a Chinese patient with dementia, ataxia, deafness, and paraplegia and a heterozygous stop loss variant (p.*267Leuext*11)
ClinVar: SCV002059726.1 - likely pathogenic stop loss variant (c.800G>T p.Ter267Leu) similar to the FBD variant reported in an individual affected with ABri amyloidosis by Centogene AG
PMID: 20385796 - mouse model of Danish variant demonstrates amyloid deposition in brain (to a lesser extent in the cerebellum), and increased anxiety.
Sources: Expert list

Created: 22 Nov 2022, 4:59 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cerebral amyloid angiopathy MONDO:0005620

Publications

• 10391242
• 10781099
• 20385796
• 33814452

Mode of pathogenicity
Other

Variants in this GENE are reported as part of current diagnostic practice