One of several autosomal dominant diseases associated with defects in integral membrane protein 2B (ITM2B); also known as familial British dementia (FBD). See the human disease model report for cerebral amyloid angiopathy, ITM2B-related (FBhh0000245).
Variant(s) implicated in human disease tested (as transgenic human gene, ITM2B): the British variant form [*267R (+11aa)] has been introduced into flies; this mutation results read-through of the normal stop codon and a carboxy extension of the protein.
[updated Jul. 2017 by FlyBase; FBrf0222196]
Cerebral amyloid angiopathy (CAA), or cerebroarterial amyloidosis, refers to a pathologic process in which amyloid protein progressively deposits in cerebral blood vessel walls with subsequent degenerative vascular changes that usually result in spontaneous cerebral hemorrhage, recurrent headaches, ischemic lesions, hemorrhagic strokes, and progressive dementia (Revesz et al., 2003; pubmed: 14533778). [from MIM:605714; 2017.06.02]
Cerebral amyloid angiopathy (CAA) refers to the deposition of β-amyloid in the walls of the blood vessels of the central nervous system. It is a component of any disorder in which amyloid is deposited in the brain; it is not associated with systemic amyloidosis. While often asymptomatic, CAA may lead to dementia, intracranial hemorrhage, or transient neurologic events. [http://emedicine.medscape.com/article/1162720-overview, 2017.07.14]
[CEREBRAL AMYLOID ANGIOPATHY, ITM2B-RELATED, 1](https://omim.org/entry/176500)
[INTEGRAL MEMBRANE PROTEIN 2B; ITM2B](https://omim.org/entry/603904)
In one family studied, onset occurred between 40 and 60 years of age with early onset of spasticity with increased deep tendon reflexes and tone. Muscular rigidity was present only late in the illness. Mental deterioration was progressive, with survival as long as 13 years after onset. [from MIM:176500; 2016.04.12]
This disorder is caused by mutation in the integral membrane protein 2B (ITM2B) gene (also called the BRI2 gene); it is inherited as an autosomal dominant. The specific genetic lesion in cerebral amyloid angiopathy, ITM2B-related, 1 is a single base substitution at the stop codon of ITM2B (X267R), generating a longer open reading frame (277aa vs. the normal 266aa). [from MIM:176500; 2016.04.12]
Like Alzheimer disease, cerebral amyloid angiopathy, ITM2B-related, 1 and 2 are associated with amyloid deposition and neurodegeneration in the central nervous system. [from MIM:117300; 2016.04.12]
Pathological findings in the brain are similar to but distinguishable from that seen in Alzheimer disease. [from MIM:176500; 2016.04.12]
Many to one: 3 human to 1 Drosophila; additional human orthologous genes are ITM2A and ITM2C.
