婴儿神经轴索营养不良1例临床和基因变异分析

Infantile neuroaxonal dystrophy and PLA2G6 gene mutation analysis:a case report

目的探讨婴儿神经轴索营养不良(INAD)的临床特点和PLA2G6基因变异特征。方法回顾分析1例经基因检测确诊的INAD患儿的临床资料。结果患儿,女性,2岁。1岁7个月发病,临床表现为精神运动发育倒退、肌张力减低、病理征阳性。头颅磁共振成像(MRI)示双侧小脑萎缩;肌电图未见异常;2 h视频脑电图未见异常。基因检测示患儿PLA2G6基因两处变异c.150_153 del、c.799T>C,分别遗传自母亲和父亲,为复合杂合变异,均未在正常人群中检测到。c.150_153 del变异导致从第51号苏氨酸开始的氨基酸合成发生改变,并在改变后的第30个氨基酸终止(p.Pro51Thrfs*30),为移码变异;c.799T>C变异致第267号氨基酸由半胱氨酸变为精氨酸(p.Cys 267 Arg),为错义变异;Poly-Phen 2预测上述变异可导致蛋白质功能受到影响。结论二代测序技术可准确检测PLA2G6基因变异,扩大了中国INAD患者的基因变异谱。

Objective To explore the clinical characteristics of infantile neuroaxonal dystrophy(INAD)and the feature of PLA2G6 gene mutation.Method The clinical data of an child with INAD confirmed by gene detection were retrospectively analyzed.Results The patient was a 2 year old female with an onset age of 1 year and 7 months.The clinical manifestations were psychomotor regression,hypotonia and positive pathological signs.Head MRI showed bilateral cerebellar atrophy.Electromyography and 2 h video electroencephalogram showed no abnormality.Genetic testing showed two mutations of c.150_153 del and c.799 T>C in PLA2G6 gene,which were inherited from mother and father,respectively.These were complex heterozygous variants,none of which have been detected in the normal population.The mutation of c.150_153 del resulted in a change in the synthesis of amino acids starting from threonine 51 and terminating at the 30 th amino acid after the change(P.P.51 thrfs*30),which is a frameshift mutation.The mutation of c.799 T>C resulted in the change of 267 th amino acid from cysteine to arginine(p.Cys 267Arg),which was a missense mutation.Poly-Phen 2 predicted that the mutations mentioned above could affect the protein function.Conclusion The second generation sequencing technology can accurately detect the mutation of PLA2G6 gene.This study expanded the gene mutation spectrum of INAD patients in China.