Analysis ofCYP2U1 gene variants in a child with Hereditary spastic paraplegia type 56
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目的 分析1例表现为遗传性痉挛性截瘫(HSP)患儿的临床表型与遗传学特征。 方法 选取在2020年8月10日因"发现双下肢尖足2年"于郑州大学第三附属医院就诊的1例HSP女性患儿作为研究对象，收集其相关临床资料。采集患儿及其父母的外周血样，提取基因组DNA，进行家系全外显子组测序(trio-WES)，对候选变异进行Sanger测序家系验证。利用生物信息学软件分析变异位点氨基酸序列的进化保守性。 结果 患儿为2岁10月龄女性，临床表现为下肢肌张力增高、尖足、认知语言落后。Trio-WES检测提示患儿CYP2U1基因(NM_183075.3)第2外显子存在父源的c.865C>T (p.Gln289*)和母源的c.1126G>A (p.Glu376Lys)复合杂合变异，其中c.1126G>A (p.Glu376Lys)位点的氨基酸序列在多个物种中高度保守。根据美国医学遗传学与基因组学学会相关指南，c.865C>T变异评级为可能致病变异(PVS1+PM2_Supporting)，c.1126G>A变异评级为临床意义不明变异(PM2_Supporting+PM3+PP3)。 结论 该患儿被确诊为CYP2U1基因变异所致的遗传性痉挛性截瘫56型。新变异的检出丰富了CYP2U1基因的变异谱。 Objective To analyze the clinical phenotype and genetic characteristics of a child with Hereditary spastic paraplegia (HSP). Methods A child with HSP who was admitted to the Third Affiliated Hospital of Zhengzhou University on August 10, 2020 due to discovery of tiptoeing for 2 years was selected as the study subject, and relevant clinical data was collected. Peripheral blood samples of the child and her parents were collected for the extraction of genomic DNA. And trio-whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing. Bioinformatic software was used to analyze the conservation of variant sites. Results The child was a 2-year-and-10-month-old female with clinical manifestations including increased muscle tone of lower limbs, pointed feet, and cognitive language delay. Trio-WES results showed that she had harbored compound heterozygous variants of c. 865C>T (p.Gln289*) and c. 1126G>A (p.Glu376Lys) of theCYP2U1 gene. And the corresponding amino acid for c. 1126G>A (p.Glu376Lys) is highly conserved among various species. Based on guidelines from the American College of Medical Genetics and Genomics, the c. 865C>T was predicted as a pathogenic variant (PVS1+ PM2_Supporting), and c. 1126G>A was rated as a variant of uncertain significance (PM2_Supporting+ PM3+ PP3). Conclusion The child was diagnosed with HSP type 56 due to compound variants of the CYP2U1 gene. Above findings have enriched the mutation spectrum of the CYP2U1 gene.
Objective To analyze the clinical phenotype and genetic characteristics of a child with Hereditary spastic paraplegia (HSP). Methods A child with HSP who was admitted to the Third Affiliated Hospital of Zhengzhou University on August 10, 2020 due to discovery of tiptoeing for 2 years was selected as the study subject, and relevant clinical data was collected. Peripheral blood samples of the child and her parents were collected for the extraction of genomic DNA. And trio-whole exome sequencing (trio-WES) was carried out. Candidate variants were verified by Sanger sequencing. Bioinformatic software was used to analyze the conservation of variant sites. Results The child was a 2-year-and-10-month-old female with clinical manifestations including increased muscle tone of lower limbs, pointed feet, and cognitive language delay. Trio-WES results showed that she had harbored compound heterozygous variants of c. 865C>T (p.Gln289*) and c. 1126G>A (p.Glu376Lys) of theCYP2U1 gene. And the corresponding amino acid for c. 1126G>A (p.Glu376Lys) is highly conserved among various species. Based on guidelines from the American College of Medical Genetics and Genomics, the c. 865C>T was predicted as a pathogenic variant (PVS1+ PM2_Supporting), and c. 1126G>A was rated as a variant of uncertain significance (PM2_Supporting+ PM3+ PP3). Conclusion The child was diagnosed with HSP type 56 due to compound variants of the CYP2U1 gene. Above findings have enriched the mutation spectrum of the CYP2U1 gene.
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