The number of gene mutations involved in the hereditary spastic paraplegias is rapidly growing due to the expansion of the frontiers of genomic research by next-generation DNA sequencing platforms. Nevertheless, a comprehensive genetic diagnosis method remains yet unavailable for these diseases. In the current research, an 8-year-old boy with short stature and developmental delay impairment, from a nonconsanguineous family, was referred to our genetic lab. Firstly, based on the physician recommendation, the patient was evaluated by tandem mass spectrometry (MS/MS) for the quantitative examination of amino acids, and then the patient was genetically investigated by karyotype analysis and whole-exome sequencing (WES) technique. Subsequently, targeted Sanger sequencing was applied to confirm the presence of the candidate variant in all the members of the family and screening the other patients for Troyer syndrome. Analysis of inherited metabolic disorders by tandem MS/MS showed the state of all the family members as normal and also karyotyping indicated no chromosomal aberration in the patient. Further investigation by WES technique indicated a homozygous missense variant in the SPG20 gene, c.1006C>T. Targeted sequencing result of the mutation confirmed homozygote state for the affected case and a heterozygote genotype for his parents. The mutation was classified as pathogenic. Detection of novel variants especially pathogenic variant in the SPG20 gene was associated with Troyer syndrome, which encodes a multifunctional protein termed Spartin, assist in improving genotype‒phenotype correlation of genetic variants and may facilitate initial diagnosis of Troyer syndrome.

中文翻译：

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与 Troyer 综合征相关的 SPG20 基因的新错义突变 (c.1006C>T)

由于下一代 DNA 测序平台扩展了基因组研究的前沿，遗传性痉挛性截瘫中涉及的基因突变数量正在迅速增加。然而，对于这些疾病，仍然没有全面的基因诊断方法。在当前的研究中，一名来自非血缘家庭的身材矮小和发育迟缓的 8 岁男孩被转介到我们的基因实验室。首先，根据医生的建议，对患者进行串联质谱（MS/MS）氨基酸定量检测，然后通过核型分析和全外显子组测序（WES）技术对患者进行基因调查。随后，应用靶向 Sanger 测序来确认所有家庭成员中是否存在候选变异，并筛查其他患者的 Troyer 综合征。串联 MS/MS 对遗传性代谢紊乱的分析显示所有家庭成员的状态都正常，而且核型分析表明患者没有染色体畸变。WES 技术进一步研究表明 SPG20 基因中存在纯合错义变异，c.1006C>T。突变的靶向测序结果证实了受影响病例的纯合子状态和其父母的杂合子基因型。该突变被归类为致病性。检测到 SPG20 基因中的新变异特别是致病变异与 Troyer 综合征有关，该综合征编码一种称为 Spartin 的多功能蛋白质，