共济失调伴眼动失用2型患者一家系临床特征及基因突变分析

Clinical and genetic studies of a pedigree with SETX gene-related ataxia with oculomotor apraxia type 2

目的探讨SETX基因突变相关的共济失调伴眼动失用2型一家系患者的临床特征及基因突变特点。方法总结中日友好医院神经科门诊收治的一来自非近亲结婚家系的共济失调家系患者的临床特征及辅助检查结果。应用全外显子测序技术对患者进行基因检测,结合一代测序对患者及家系成员进行突变位点验证。结果先证者表现为进行性步态不稳、构音障碍、眼动失用、轻度认知功能减退,血清甲胎蛋白水平升高,肌电图检查提示多发性周围神经病,头颅磁共振平扫可见明显小脑萎缩。全外显子测序发现该患者存在复合杂合突变c.5591_5592delAA(p.Q1864Rfs*34)及c.6638C>T(p.P2213L),一代测序家系验证显示两个突变分别来自其父母。结论共济失调伴眼动失用2型在中国人群罕见,通过特征性的临床表型结合全外显子测序技术有助于快速诊断该病。

Objective To investigate the clinical characteristics and pathogenic variants of SETX gene related ataxia with oculomotor apraxia type 2(AOA2).Methods We summarized clinical features,detailed auxiliary examinations of a female cerebellar ataxia patient,she was from a non-consanguineous family and was admitted to the Department of Neurology of China-Japan friendship hospital.We conducted whole exome sequencing(WES)of the proband,potential pathogenic variants were validated by Sanger sequencing and verified in her asymptomatic family members.Results The proband exhibited progressive unsteady walk,dysarthria,oculomotor apraxia and mild cognitive decline,serumα-fetoprotein was elevated,electromyography revealed peripheral neuropathy,and brain MRI showed remarkable cerebellar atrophy.Through WES,we identified compound heterozygous mutations c.5591_5592delAA(p.Q1864Rfs*34)and c.6638C>T(p.P2213L)of SETX gene in this patient,and they were respectively inherited from her father and mother.Conclusions AOA2 is rare in Chinese population,characterized clinical phenotypes combined with WES allows the rapid diagnosis of this disease.