WES in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease
WES in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease
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DOI：
10.1111/cge.12730
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发表时间：
2016-08-01
影响因子：
3.5
通讯作者：
Minetti, C.
中科院分区：
文献类型：
--
作者：
Covone, A. E.;Fiorillo, C.;Minetti, C.
我们对一个患有进行性运动神经元疾病的16岁女孩的三人家庭进行了全外显子组测序。无家族史，父母无血缘关系。我们的外显子组分析表明，先证者作为一个复合杂合子的两个错义变异的TECPR2基因根据隐性遗传模式。据报道，TECPR2基因是自噬的正调节因子，自噬是维持神经元稳态和存活的重要机制，在主要的成人和儿童神经退行性疾病中起关键作用。在此基因的变异已被发现负责最近描述的遗传性痉挛性截瘫的形式称为SPG49在以前的两个报告。我们建议，这两种变体引起的氨基酸取代，p.Leu684Val和p.Thr903Met，在反相复合杂合子的形式继承，可以负责在我们的病人中观察到的表型。我们还考虑了SPG7基因中杂合变体的可能贡献。桑格测序证实了包括患者未受影响的兄弟在内的家谱中的变异分离。
We have performed whole-exome sequencing in a family trio with a 16-year-old girl suffering of progressive motor neuron disease. There was no family history of the disease and no parental consanguinity. Our exome analysis indicated the proband as a compound heterozygote for two missense variants in the TECPR2 gene according to a recessive mode of inheritance. The TECPR2 gene has been reported as a positive regulator of autophagy which is an essential mechanism for maintaining neuron homeostasis and survival and plays a key role in major adult and pediatric neurodegenerative diseases. Variants in this gene have been found responsible for a recently described form of hereditary spastic paraplegia called SPG49 in two previous reports. We propose that both variants causing amino acid substitution, p.Leu684Val and p.Thr903Met, inherited in trans-phase compound heterozygote form, can be responsible for the phenotype observed in our patient. We also consider the possible contribution of a heterozygous variant in the SPG7 gene. Sanger sequencing confirmed the segregation of variants within the family tree including the patient's unaffected brother.