De novo cerebral cavernous malformations with PIK3CA somatic mutation and EPHB4 germline mutation in a child with multiple developmental venous anomalies and cutaneous vascular malformations
机构：[1]Capital Med Univ, China Int Neurosci Inst, Dept Neurosurg, Xuanwu Hosp, Beijing 100053, Peoples R China首都医科大学宣武医院[2]Chinese Acad Med Sci & Peking Union Med Coll, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovasc Dis, Beijing, Peoples R China
Cavernous malformations (CM) that arise in the central nervous system have long been considered congenital, while there are many reports of de novo non-familial-type CM adjacent to developmental venous anomalies (DVA) or after radiation. The mechanisms that cause de novo formations of sporadic cavernous malformation (CM) still remain unknown and purely speculative. We report a case of de novo cerebral CM in a child with multiple developmental venous anomalies and cutaneous vascular malformations. Histological examination and whole-exome sequencing (WES) was performed on a fresh-frozen tissue sample of the CM. WES revealed 2 missense non-synonymous variants in two genes, EPHB4 and PIK3CA. The mutant allele of EPHB4 (NM_004444.4: c.1840 T > C, p.Y614H) appeared in 248/469 WES reads (allele frequency, 52.88%), which suggested the mutation a germline one. PIK3CA (NM_006218.2) somatic mutations were found in exon 9: c.1624G > A (p.Glu542Lys) with variant frequency of 2.2% (2/89 WES reads). We did not find any non-synonymous mutations of the three CCM genes (KRIT1, CCM2, and PDCD10) in this patient. Our findings suggested that the combination of gain of function in PIK3CA and loss of function in EPHB4 may play an important role in the pathogenesis of CM, which can develop in acquired form like tumorigenesis.
基金：
National Natural Science Foundation of China [81971113]
第一作者机构：[1]Capital Med Univ, China Int Neurosci Inst, Dept Neurosurg, Xuanwu Hosp, Beijing 100053, Peoples R China
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推荐引用方式(GB/T 7714)：
Ren Jian,Xiao Xiao,Tu Tianqi,et al.De novo cerebral cavernous malformations with PIK3CA somatic mutation and EPHB4 germline mutation in a child with multiple developmental venous anomalies and cutaneous vascular malformations[J].CHILDS NERVOUS SYSTEM.2023,39(1):265-267.doi:10.1007/s00381-022-05570-z.
APA：
Ren, Jian,Xiao, Xiao,Tu, Tianqi,Opoku, Isabella,Zhang, Hongqi&Zeng, Gao.(2023).De novo cerebral cavernous malformations with PIK3CA somatic mutation and EPHB4 germline mutation in a child with multiple developmental venous anomalies and cutaneous vascular malformations.CHILDS NERVOUS SYSTEM,39,(1)
MLA：
Ren, Jian,et al."De novo cerebral cavernous malformations with PIK3CA somatic mutation and EPHB4 germline mutation in a child with multiple developmental venous anomalies and cutaneous vascular malformations".CHILDS NERVOUS SYSTEM 39..1(2023):265-267
