一例家族性颅内海绵状血管瘤基因新突变位点报道及文献复习

目的：对一例家族性颅内海绵状血管瘤（FCCM）家系进行临床诊断、治疗及遗传学分析,并复习相关文献。方法：对先证者及其亲属收集临床资料及应用全外显子组测序（WES）技术进行基因分析。结果：先证者及其大儿子临床诊断为 FCCM,且先证者合并皮肤血管畸形,其 CCM1/KRIT1 基因均发现 c.1307_1308insT的杂合核苷酸变异,该变异导致从第436号氨基酸亮氨酸（Leu）开始的氨基酸合成发生改变,并在改变后的第6个氨基酸终止（p.Leu436PhefsTer6）,为移码变异。其他无症状的家族成员,均未见该基因突变。该位点突变在之前未见报道。先证者为双侧颞叶海绵状血管瘤,治疗相对困难,经两次手术后疗效欠佳,仍需密切随访。结论：FCCM患者CCM1/KRIT1基因有新的突变位点;先证者临床表现除顽固性癫痫发作外,合并CCM1基因突变导致的皮肤血管畸形;先证者表现为多发海绵状血管瘤（CCMs）,双侧颞叶为可疑致痫灶,经两次手术治疗后效果欠佳。

Case Report of Familial Cerebral Cavernous Hemangioma with New Mutation Site andLiterature Review

A case of familial cerebral cavernous hemangioma (FCCM) was clinically diagnosed,treated, and genetically analyzed, and relevant literature was reviewed. Methods: The clinical data of the indexpatient and her relatives were analyzed, and their DNA was sequenced by whole exome sequencing (WES).Results: The index patient and her elder son were clinically diagnosed with FCCM, and the proband had skinvascular malformations. They both carried the c.1307_1308insT heterozygous mutation of the CCM1/KRIT1gene, which resulted in a frameshift mutation starting from amino acid leucine (Leu) no. 436 and terminating atthe sixth amino acid (p.Leu436PhefsTer6). Other asymptomatic family members did not have this mutation.This mutation had not been previously reported. The index patient had bilateral cavernous hemangiomas of thetemporal lobe which were difficult to treat. Two surgeries were performed yielding subpar results, and closeclinical follow-up was still needed. Conclusion: A new mutation site of CCM1/KRIT1 was discovered in theFCCM patients. In addition to intractable epileptic seizures, the proband presented skin vascular malformationscaused by the CCM1 gene mutation. The proband had multiple cavernous hemangioma (CCMs) and suspectedepileptogenic foci located in the bilateral temporal lobes; two surgical treatments were performed but wereineffective.