One of several autosomal dominant diseases associated with defects in integral membrane protein 2B (ITM2B); also known as familial Danish dementia (FDD). 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 Danish variant form (NM_021999. 4:c.786_795dupTTTAATTTGT ) have been introduced into flies; this mutation results in 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, 2](https://omim.org/entry/117300)
[INTEGRAL MEMBRANE PROTEIN 2B; ITM2B](https://omim.org/entry/603904)
Cataracts are typically the first manifestation of cerebral amyloid angiopathy, ITM2B-related, 2, starting before the age of 30, whereas impaired hearing usually develops 10 to 20 years later. Cerebellar ataxia occurs shortly after the age of 40, followed by paranoid psychosis and dementia 10 years later. Most patients die in their fifth to sixth decade of life. [from MIM:117300; 2016.04.12]
This disorder is caused by mutation in the integral membrane protein 2B (ITM2B) gene (also called the BRI2 gene); it is inheritied as an autosomal dominant. [from MIM:176500; 2016.04.12]
The specific genetic lesion in cerebral amyloid angiopathy, ITM2B-related, 2 is a 10-bp duplication at nt795, which is near the end of the CDS; results in a carboxy extension. [from MIM:603904; 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]
Many to one: 3 human to 1 Drosophila; additional human orthologous genes are ITM2A and ITM2C.
