BIO17362-D1

Biomarker and methods for predicting intracranial aneurysm

The present invention relates to a method for predicting the risk of having or developing Intracranial aneurysms (IA) in a subject, by identifying at least one mutation in an angiogenic protein, such as Angiopoietin-Like 6 (ANGPTL6). In particular, inventors identified one rare nonsense variant (c.1378A>T) in the last exon of the ANGPTL6 gene which encodes a circulating pro-angiogenic factor mainly secreted from the liver shared by the 4 tested affected members of a large pedigree with multiple IA carriers. They showed a 50% reduction of ANGPTL6 serum concentration in heterozygous c.1378A>T carriers compared to non-carrier relatives, due to the non-secretion of the truncated protein produced by the c.1378A>T transcripts. Sequencing ANGPTL6 in a series of 94 additional index cases with familial IA identified 3 other rare coding variants in 5 cases. They observed a higher rate of individuals with a history of high blood pressure among affected versus healthy carriers of ANGPTL6 variants, suggesting that ANGPTL6 could trigger cerebrovascular lesions when combined with other risk factors such as hypertension. Altogether, their results indicate that rare coding variants in ANGPTL6 are causally related to familial forms of IA.

Scientific publication(s):
Am J Hum Genet., 2018 Jan 4, Bourcier R. et al., Rare Coding Variants in ANGPTL6 Are Associated with Familial Forms of Intracranial Aneurysm, doi: 10.1016/j.ajhg.2017.12.006


Keywords : PCR, Q-PCR, Sequencing, Genomics, Sequencing, Diagnostic, Risk Predisposition in Intracranial aneurysms ,
Patent Application number : EP17306466.8
Patent Application date : 2017-10-24
Multidisciplinary field : -
Technology/Engineering : -
Technological Platform : Genomics, Sequencing
Rare disease : -
Second indication : -
Inventors : Richard REDON
Publications : -

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