AUTHOR=Wang Kang , Wu Dengchang , Zhang Baorong , Zhao Guohua 

TITLE=Novel KRIT1/CCM1 and MGC4607/CCM2 Gene Variants in Chinese Families With Cerebral Cavernous Malformations

JOURNAL=Frontiers in Neurology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.01128

DOI=10.3389/fneur.2018.01128

ISSN=1664-2295

ABSTRACT=<p>Familial cerebral cavernous malformations (CCMs) are autosomal dominant disorders characterized by hemorrhagic strokes, recurrent headache, epilepsy, and focal neurological deficits. Genetic variants in <italic>KRIT1/CCM1, MGC4607/CCM2</italic>, and <italic>PDCD10/CCM3</italic> genes contribute to CCMs. The clinical information of two Chinese families with CCMs was collected. MRI and video-electroencephalography were performed. Genetic variants of <italic>CCM1, CCM2</italic>, and <italic>CCM3</italic> genes were investigated by exome sequencing. The patients were presented with recurrent epilepsy or headache. Susceptibility-weighted images of brains showed many dark dots, while video-electroencephalography revealed many spikes from multiple brain regions of patients. Exome sequencing revealed a novel <italic>CCM1</italic> genetic variant (c.1599_1601TGAdel, p.Asp533del) and a novel <italic>CCM2</italic> genetic variant (c.773delA, p.K258fsX34) in Family one and Family two, respectively; cosegregation existed in these two families. The two family members presented typical CCMs symptoms. These two novel genetic variants in <italic>CCM1</italic> and <italic>CCM2</italic> genes were the causation of CCM in the two Chinese families, and our data enriched the genetic variant spectrum of CCM genes.</p>