Jiang Xiao-Yu, Zhang Ying, Yin Xiang, Nan Di, Wang Xu, Feng Jia-Chun, Miao Jing
First Hospital, Jilin University, Changchun, Jilin, China.
The First Hospital of Jilin University, China.
Ther Adv Neurol Disord. 2020 Feb 3;13:1756286420902664. doi: 10.1177/1756286420902664. eCollection 2020.
Cerebral cavernous malformation (CCM), especially the familial form, is a relatively rare congenital and occult vascular disease of the central nervous system. The familial form of CCM has been linked to three different genes: //, and /; however, the genetic basis of CCM is not well understood. The / is the most recent gene to be identified that results in worse clinical symptoms. Early diagnosis and treatment is important for patient prognosis.
The proband is a 38-year-old male who has been suffering from weakness in the limbs for 7 months. Investigation of his family history revealed that his mother also suffered from limbs paralysis and had been bedridden for a long time. His older brother suffered from headache for years, whereas his younger brother was asymptomatic. Brain computed tomography analysis of all family members showed multiple high-density shadows. Subsequently, magnetic resonance imaging analysis identified more prominent and similar multiple intracranial lesions in all family members. The lesions were hypo-intense, or showed mixed signs on T1-weighted imaging, and were significantly more intense on T2-weighted imaging. To understand the genetic basis of the disease in the family, DNA sequencing analysis was performed. A novel deletion mutation in the / gene was identified in the proband and his relatives. The deletion resulted in a frameshift mutation and premature termination of translation of the protein, and potentially caused the disease in this family.
Our study identified a novel / heterozygous deletion (c.165delT) associated with CCM. This finding expands the gene mutation profile, which will be beneficial for genetic counseling and clinical therapy.
脑海绵状血管畸形（CCM），尤其是家族性CCM，是一种相对罕见的中枢神经系统先天性隐匿性血管疾病。家族性CCM与三个不同的基因相关：//和/；然而，CCM的遗传基础尚未完全明确。/是最近发现的与更严重临床症状相关的基因。早期诊断和治疗对患者预后很重要。
先证者是一名38岁男性，肢体无力7个月。家族史调查显示，他的母亲也患有肢体瘫痪，长期卧床。他的哥哥多年来一直头痛，而他的弟弟无症状。对所有家庭成员进行脑部计算机断层扫描分析，显示多个高密度阴影。随后，磁共振成像分析在所有家庭成员中发现了更明显且相似的多个颅内病变。这些病变在T1加权成像上呈低信号或表现为混合信号，在T2加权成像上信号明显增强。为了解该家族疾病的遗传基础，进行了DNA测序分析。在先证者及其亲属中发现了/基因的一种新的缺失突变。该缺失导致移码突变和蛋白质翻译提前终止，并可能导致了这个家族的疾病。
我们的研究发现了一种与CCM相关的新的/杂合缺失（c.165delT）。这一发现扩展了/基因突变谱，将有利于遗传咨询和临床治疗。
