KRIT1基因p.L436fs突变导致脑海绵状血管瘤一家系

Cerebral cavernous hemangioma in a family with mutation p.L436fs in KRIT1 gene

目的通过对脑海绵状血管瘤的一家系研究,了解家族性海绵状血管瘤的临床表现及致病基因突变位点。方法收集2019年4月入住河南科技大学第一附属医院神经内科的脑海绵状血管瘤的一家系的临床资料,根据临床表现、头颅磁共振成像(MRI)平扫+弥散加权成像+磁敏感加权成像表现和Zabramski分型标准诊断为脑海绵状血管瘤1型,对其进行基因测序。结果先证者为58岁女性,以头晕、头痛为主要症状,先证者女儿、儿子无临床症状,先证者孙女临床表现为脑出血、癫痫发作。先证者及其家系成员头颅MRI可见多发海绵状血管瘤,通过基因检测确定此家系为家族性脑海绵状畸形1型,与根据头颅MRI的表现和Zabramski分型结果一致,家族性脑海绵状畸形1型致病基因突变位点为KRIT1基因p.L436fs,目前尚无家族性脑海绵状血管瘤1型的该基因突变位点的完整报告。结论本研究发现了此家系中脑海绵状畸形1型,KRIT1基因突变位点为p.L436fs,对家族性海绵状血管瘤的临床表现及致病基因突变位点有了更全面的了解。

Objective To investigate the clinical manifestations and pathogenic gene mutation sites of familial cavernous hemangioma by a pedigree study of this disease.Methods A family of cerebral cavernous hemangioma who was admitted to the Department of Neurology of the First Affiliated Hospital of Henan University of Science and Technology in April 2019 was diagnosed as cerebral cavernous hemangioma type 1 based on clinical manifestations and head magnetic resonance imaging(MRI),diffusion weighted imaging and susceptibility weighted imaging screening.According to Zabramski classification criteria,the family′s clinical data were collected and genes were sequenced.Results A 58-year-old female proband had dizziness and headache as the main symptoms,her daughter and son had no clinical symptoms,and her granddaughter had clinical manifestations of cerebral hemorrhage and seizures.The proband and her family members showed multiple cavernous hemangioma on cranial MRI,and the p.L436fs mutation in the KRIT1 gene of familial cerebral cavernous malformation type 1 was confirmed through genetic examination,which was consistent with the Zabramski typing results based on head MRI.The mutation site of the familial spongiform malformation type 1 pathogenic gene was found to be p.L436fs in KRIT1 gene,which has not been reported in familial cerebral cavernous hemangioma type 1 until now.Conclusion A new p.L436fs mutation of KRIT1 gene was found in familial cerebral cavernous malformation type 1,which expands understanding of the clinical manifestations and pathogenic gene mutation sites of familial cavernous hemangioma.