期刊
JOURNAL OF CLINICAL MEDICINE
卷 11, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/jcm11102685
关键词
hereditary hemorrhagic telangiectasia; cerebrovascular malformations; arteriovenous malformations; genetics; gene variants; ENG; ACVRL1
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder caused by mutations of the endoglin (ENG) or the activin A receptor-like type 1 (ACVRL1) gene. Cerebrovascular malformations in HHT patients were found to be heterogeneous, with various phenotypes including arteriovenous malformations, intracranial aneurysms, developmental venous anomalies, and cavernous angiomas. The variants of ENG and ACVRL1 genes also showed wide heterogeneity.
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder caused, in more than 80% of cases, by mutations of either the endoglin (ENG) or the activin A receptor-like type 1 (ACVRL1) gene. Several hundred variants have been identified in these HHT-causing genes, including deletions, missense and nonsense mutations, splice defects, duplications, and insertions. In this study, we have analyzed retrospectively collected images of magnetic resonance angiographies (MRA) of the brain of HHT patients, followed at the HHT Center of our University Hospital, and looked for the distribution of cerebrovascular phenotypes according to specific gene variants. We found that cerebrovascular malformations were heterogeneous among HHT patients, with phenotypes that ranged from classical arteriovenous malformations (AVM) to intracranial aneurysms (IA), developmental venous anomalies (DVA), and cavernous angiomas (CA). There was also wide heterogeneity among the variants of the ENG and ACVRL1 genes, which included known pathogenic variants, variants of unknown significance, variants pending classification, and variants which had not been previously reported. The percentage of patients with cerebrovascular malformations was significantly higher among subjects with ENG variants than ACVRL1 variants (25.0% vs. 13.1%, p < 0.05). The prevalence of neurovascular anomalies was different among subjects with different gene variants, with an incidence that ranged from 3.3% among subjects with the c.1231C > T, c.200G > A, or c.1120C > T missense mutations of the ACVRL1 gene, to 75.0% among subjects with the c.1435C > T missense mutation of the ACVRL1 gene. Further studies and larger sample sizes are required to confirm these findings.
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