C19orf12基因p.Gly58Ser纯合突变导致线粒体膜蛋白相关性神经变性病1例  

A case of mitochondrial membrane protein-associated neurodegeneration caused by C19orf12 p.Gly58Ser mutation

作　　者：刘超 王罗俊 邓艳春 Liu Chao;Wang Luojun;Deng Yanchun(Department of Neurology,the First Affiliated Hospital of Air Force Military Medical University,Xifan 710032,China)

机构地区：[1]空军军医大学第一附属医院神经内科,西安710032

出　　处：《中华神经科杂志》2022年第6期634-639,共6页Chinese Journal of Neurology

基　　金：科技部国家重点研发计划(2017YFC0907702)。

摘　　要：脑组织铁沉积性神经变性病(NBIA)是一组罕见的神经系统遗传性疾病,以脑组织不同程度的铁代谢异常和过量铁沉积为特征,其中最常见症状为锥体外系症状,亦可合并不同程度的锥体束、小脑、周围神经系统、自主神经系统、精神认知、视觉功能障碍。文中报道1例2020年12月于西京医院神经内科就诊的NBIA患者,分析其临床特征,并通过全外显子测序技术进行基因突变筛查,根据美国医学遗传学与基因组学学会(ACMG)指南做致病性分析。患者为13岁男性,4岁起病,呈慢性病程,进行性加重,首发症状为痉挛步态,随病情进展出现智能减退、构音障碍、饮水呛咳和视力下降。头颅磁共振成像检查可见视神经萎缩,苍白球及黑质T2WI、液体衰减反转恢复序列、弥散加权成像及磁敏感成像呈对称性低信号,无泛酸激酶相关神经变性中普遍存在的"虎眼征"。患者经全外显子基因检测可见C19orf12基因第2号外显子c.172G>A纯合突变,导致第58位氨基酸由甘氨酸变为色氨酸(p.Gly58Ser),其父亲和母亲为姨表兄妹(近亲婚育),均携带该位点杂合变异。该突变位点未见文献报道,为新突变,根据ACMG指南考虑为可能致病变异。该位点保守性预测提示高度保守。该患者最终被诊断线粒体膜蛋白相关性神经变性病(MPAN)即NBIA4型,丰富了MPAN的突变数据库,为该病的进一步研究提供了依据。Neurodegeneration with brain iron accumulation(NBIA)is a group of rare genetic diseases of nervous system.NBIA is characterized by varying degrees of abnormal iron metabolism and excessive iron deposition in brain tissue.The most common symptoms of NBIA are extrapyramidal symptoms.NBIA can also be associated with varying degrees of dysfunction of the pyramidal tract,cerebellum,peripheral nervous system,autonomic nervous system,mental cognition and vision functions.A patient with NBIA admitted to the Department of Neurology of Xijing Hospital in December 2020 was collected and analyzed for clinical features.Whole exome sequencing(WES)was employed to gene mutation screening,and pathogenicity analysis was performed according to the American College of Medical Genetics and Genomics(ACMG)guideline.The patient was a 13-year-old male with a chronic course of disease that began at the age of 4.The first symptom was spastic gait.With the progress of the disease,the patient developed mental retardation,arrhythmia,coughing from drinking water and loss of vision.Magnetic resonance imaging of the head showed atrophy of the optic nerve and hypointensity signal in bilateral substantia nigra and globus pallidus on T2WI,fluid attenuated inversion recovery sequency,diffusion weighted imaging and susceptibility weighted imaging without"tiger eye sign"which was commonly found in pantothenate kinase associated neurodegeneration.The homozygous mutation c.172G>A(p.Gly58Ser)was found through WES.The proband′s father and mother are cousins(inbreeding),carried heterozygous variation of this locus.This novel mutation was not reported in mutation database.According to ACMG guideline,C19orf12 gene c.172G>A(p.Gly58Ser)was identified for possible pathogenic mutations.The conservative prediction of this locus suggests high conservatism.The final diagnosis of the patient was mitochondrial membrane protein-associated neurodegeneration(MPAN,NBIA type 4).This finding enriched the known mutation database of MPAN and provided a basis for further st

关 键 词：铁代谢障碍 神经变性疾病 突变 C19orf12基因 线粒体膜蛋白相关性神经变性病 

分 类 号：R741[医药卫生—神经病学与精神病学]