Somatic MAP3K3 mutation defines a subclass of cerebral cavernous malformation

Cerebral cavernous malformations (CCMs) are vascular disorders that affect up to 0.5% of the total population. About 20% of CCMs are inherited because of familial mutations in CCM genes, including CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10, whereas the etiology of a majority of simplex CCM-affected individuals remains unclear. Here, we report somatic mutations of MAP3K3, PIK3CA, MAP2K7, and CCM genes in CCM lesions. In particular, somatic hotspot mutations of PIK3CA are found in 11 of 38 individuals with CCMs, and a MAP3K3 somatic mutation (c.1323C>G [p.Ile441Met]) is detected in 37.0% (34 of 92) of the simplex CCM-affected individuals.

Source: The American Journal of Human Genetics - April 22, 2021 Category: Genetics & Stem Cells Authors: Jiancong Weng, Yingxi Yang, Dong Song, Ran Huo, Hao Li, Yiyun Chen, Yoonhee Nam, Qiuxia Zhou, Yuming Jiao, Weilun Fu, Zihan Yan, Jie Wang, Hongyuan Xu, Lin Di, Jie Li, Shuo Wang, Jizong Zhao, Jiguang Wang, Yong Cao Tags: Report Source Type: research