AUTHOR=Liu Zhenxing , Guo Kaikai , Hu Xuebin , Zhang Xianqin 

TITLE=Case Report: A novel heterozygous nonsense mutation in KRIT1 cause hereditary cerebral cavernous malformation

JOURNAL=Frontiers in Oncology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1141488

DOI=10.3389/fonc.2023.1141488

ISSN=2234-943X

ABSTRACT=<p>Cerebral cavernous malformation (CCM) is a vascular malformation of the central nervous system and mainly characterized by enlarged capillary cavities without intervening brain parenchyma. Genetic studies have identified three disease-causing genes (<italic>CCM1/KRIT1</italic>, <italic>CCM2/MGC4607</italic> and <italic>CCM3/PDCD10</italic>) responsible for CCM. Here, we characterized a four-generation family diagnosed with CCM and identified a novel heterozygous mutation c.1159C&gt;T, p.Q387X in <italic>KRIT1</italic> gene by whole exome sequencing and Sanger sequencing. The Q387X mutation resulted in premature termination of KRIT1 protein, which was predicted to be deleterious by the ACMG/AMP 2015 guideline. Our results provide novel genetic evidence support that <italic>KRIT1</italic> mutations cause CCM, and are helpful to the treatment and genetic diagnosis of CCM.</p>