Iruzubieta Pablo, Campo-Caballero David, Equiza Jon, Albajar Inés, Sulibarría Naroa, Sáez Raquel, Andrés Naiara, Mondragón Elisabet, Zulaica Miren, de Arce Ana, Urtasun Miguel, López de Munain Adolfo
Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián, Spain; Neuromuscular Group, Neurosciences Area, Biodonostia Research Institute, San Sebastián, Spain.
Neurology Department, Donostia University Hospital, Osakidetza, San Sebastián, Spain.
J Stroke Cerebrovasc Dis. 2021 Dec;30(12):106130. doi: 10.1016/j.jstrokecerebrovasdis.2021.106130. Epub 2021 Sep 29.
Cerebral cavernous malformations (CCMs) are dilated aberrant leaky capillaries located in the Central Nervous System. Familial CCM is an autosomal dominant inherited disorder related to mutations in KRIT1, Malcavernin or PDCD10. We show two unrelated families presenting familial CCM due to two new mutations in KRIT1 and PDCD10, producing truncated proteins. Clinical phenotype was highly variable among patients from asymptomatic individuals to diplopia, seizures or severe intracranial hemorrhage. PDCD10 patients usually show a more aggressive course and they frequently showed multiple meningiomas. This work provides evidence for the pathogenicity of two new mutations in CCM genes and supports previous findings regarding familial CCM and multiple meningiomas.
脑海绵状血管畸形（CCM）是位于中枢神经系统的扩张异常且渗漏的毛细血管。家族性CCM是一种常染色体显性遗传性疾病，与KRIT1、Malcavernin或PDCD10基因的突变有关。我们展示了两个不相关的家族，由于KRIT1和PDCD10基因中的两个新突变导致家族性CCM，产生了截短的蛋白质。临床表型在患者中差异很大，从无症状个体到复视、癫痫发作或严重颅内出血。携带PDCD10突变的患者通常病程更具侵袭性，且经常出现多发脑膜瘤。这项研究为CCM基因中两个新突变的致病性提供了证据，并支持了先前关于家族性CCM和多发脑膜瘤的研究结果。
