PubMed:30413633
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/30413633","sourcedb":"PubMed","sourceid":"30413633","source_url":"https://www.ncbi.nlm.nih.gov/pubmed/30413633","text":"PCNT point mutations and familial intracranial aneurysms.\nOBJECTIVE: To identify novel genes involved in the etiology of intracranial aneurysms (IAs) or subarachnoid hemorrhages (SAHs) using whole-exome sequencing.\nMETHODS: We performed whole-exome sequencing in 13 individuals from 3 families with an autosomal dominant IA/SAH inheritance pattern to look for candidate genes for disease. In addition, we sequenced PCNT exon 38 in a further 161 idiopathic patients with IA/SAH to find additional carriers of potential pathogenic variants.\nRESULTS: We identified 2 different variants in exon 38 from the PCNT gene shared between affected members from 2 different families with either IA or SAH (p.R2728C and p.V2811L). One hundred sixty-four samples with either SAH or IA were Sanger sequenced for the PCNT exon 38. Five additional missense mutations were identified. We also found a second p.V2811L carrier in a family with a history of neurovascular diseases.\nCONCLUSION: The PCNT gene encodes a protein that is involved in the process of microtubule nucleation and organization in interphase and mitosis. Biallelic loss-of-function mutations in PCNT cause a form of primordial dwarfism (microcephalic osteodysplastic primordial dwarfism type II), and ≈50% of these patients will develop neurovascular abnormalities, including IAs and SAHs. In addition, a complete Pcnt knockout mouse model (Pcnt -/-) published previously showed general vascular abnormalities, including intracranial hemorrhage. The variants in our families lie in the highly conserved PCNT protein-protein interaction domain, making PCNT a highly plausible candidate gene in cerebrovascular disease.","tracks":[{"project":"PubTator4TogoVar","denotations":[{"id":"30413633_0","span":{"begin":694,"end":702},"obj":"ProteinMutation"},{"id":"30413633_1","span":{"begin":707,"end":715},"obj":"ProteinMutation"},{"id":"30413633_2","span":{"begin":890,"end":898},"obj":"ProteinMutation"}],"attributes":[{"id":"30413633_0_ProteinMutation","pred":"proteinmutation","subj":"30413633_0","obj":"rs762890408"},{"id":"30413633_1_ProteinMutation","pred":"proteinmutation","subj":"30413633_1","obj":"rs144757781"},{"id":"30413633_2_ProteinMutation","pred":"proteinmutation","subj":"30413633_2","obj":"rs144757781"},{"subj":"30413633_0","pred":"source","obj":"PubTator4TogoVar"},{"subj":"30413633_1","pred":"source","obj":"PubTator4TogoVar"},{"subj":"30413633_2","pred":"source","obj":"PubTator4TogoVar"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubTator4TogoVar","color":"#ece793","default":true}]}]}}