Identification of a novel LATS1 variant associated with familial cerebral cavernous malformations in a Chinese family

Neurol Sci. 2022 Nov;43(11):6389-6397. doi: 10.1007/s10072-022-06323-1. Epub 2022 Aug 19.


Background: Cerebral cavernous malformations (CCMs) are common sporadic or hereditary vascular malformations in the central nervous system. CCM1-3 variants have been identified that are associated with the majority of familial cerebral cavernous malformations (FCCMs). However, there are still a few CCM1-3 wild-type FCCMs. The aim of the present study was to identify an additional pathogenic variant of FCCMs.

Methods: In this study, a large five-generation Chinese Han family affected by CCMs was recruited. Magnetic resonance imaging (MRI) was done for the detection of CCMs. Whole-exome sequencing (WES) was performed, and the identified variants were co-segregation analyzed by Sanger sequencing. The function of candidate variants was predicted in silico and experimental validated by angiogenesis assay in human umbilical vein endothelial cells (HUVECs) in vitro.

Results: Twenty-four family members and one healthy spouse were enrolled. We found that CCMs were exhibited on MRI in nine family members. Overall, twenty-seven candidate variants were identified using WES, and no CCM1-3 variants were detected. The missense variant in LATS1 (c.821C > T, p.Thr274Ile) was verified to be associated with the clinical and pathological phenotype of FCCMs.

Conclusion: Our findings indicated that the LATS1 variant could be a potential pathogenic factor for FCCMs in this Chinese family.

Keywords: Angiogenesis; Familial cerebral cavernous malformations; Pathogenic variant; Sanger sequencing; VEGF; Whole exome sequencing.

MeSH terms

  • China
  • Endothelial Cells / pathology
  • Hemangioma, Cavernous, Central Nervous System* / diagnostic imaging
  • Hemangioma, Cavernous, Central Nervous System* / genetics
  • Humans
  • KRIT1 Protein / genetics
  • Pedigree
  • Protein Serine-Threonine Kinases / genetics


  • KRIT1 Protein
  • Protein Serine-Threonine Kinases
  • LATS1 protein, human

Supplementary concepts

  • Familial cerebral cavernous malformation