家族性神经丝氨酸蛋白酶抑制剂包涵体脑病一家系研究

A Chinese pedigree of familial encephalopathy with neuroserpin inclusions bodies

目的报道家族性神经丝氨酸蛋白酶抑制剂包涵体脑病(FENIB)一家系的临床表现和遗传学特征,以增强对该病的认识。方法先证者因认知障碍、癫痫于2020年6月就诊于河南省人民医院神经科。对先证者及其家系亲属进行详细的病史询问、神经系统体检、家系图谱绘制。对先证者完善了头颅磁共振成像(MRI)、脑电图、脑脊液、全外显子测序等检查,对部分家系内成员行Sanger测序进行验证。通过复习相关文献,分析该病的特点。结果本家系先证者为23岁青年女性,以认知障碍、癫痫为主要表现,逐渐进展。先证者母亲及兄长在青年时期出现类似临床症状,均在数年后去世。先证者头颅MRI示双侧大脑皮质广泛萎缩。全外显子测序发现编码神经丝氨酸蛋白酶抑制剂的SERPINI1基因c.1013A>G(p.H338R)杂合错义突变。该突变位点为既往国外已报道的致病突变。家系内临床表型一致,基因突变与临床表型共分离。结论对痴呆合并癫痫、肌阵挛的青年患者,要考虑SERPINI1基因突变所致FENIB的可能。

Objective To report the clinical and genetic features of a pedigree with familial encephalopathy with neuroserpin inclusions bodies(FENIB)and to enhance the understanding of the disease.Methods The proband was admitted to Department of Neurology,Henan Provincial People′s Hospital in June 2020 due to cognitive impairment and epilepsy.Detailed medical history inquiry,physical examinations,and neuroimaging examination of the family were conducted.The proband completed the examination of brain magnetic resonance imaging(MRI),electroencephalogram(EEG),cerebrospinal fluid examinations.Whole exome sequencing and Sanger sequencing were used to screen the genetic variations in the proband.Sanger sequencing was performed in some family members to verify the mutation.Through literature review,the characteristics of the disease were summarized.Results The proband was a 23-year-old young female with progressive cognitive impairment,epilepsy as the main manifestations.Brain MRI indicated moderate atrophy of bilateral cerebral cortex.Genetic sequencing revealed a heterozygous missense mutation(c.1013A>G;p.H338R)of SERPINI1 gene encoding the neuroserine protease inhibitor protein.The proband′s mother and brother had similar clinical symptoms in adolescence.Both of them passed away several years later.This mutation was a proven pathogenic mutation for FENIB.The clinical phenotype was consistent within the family.Genotype and clinical phenotype were co-segregated.Conclusion FENIB due to SERPINI1 gene mutations should be considered in young cases of cognitive decline,epilepsy and myoclonus.