Rosello Monica, Caro-Llopis Alfonso, Orellana Carmen, Oltra Silvestre, Alemany-Albert Marta, Marco-Hernandez Ana V, Monfort Sandra, Pedrola Laia, Martinez Francisco, Tomás Miguel
Genetics Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
Neuropediatric Unit, Hospital Universitario y Politécnico La Fe, Valencia, Spain.
Pediatr Res. 2021 Aug;90(2):284-288. doi: 10.1038/s41390-020-01250-3. Epub 2020 Nov 11.
Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent research studies focused on genetic diagnosis in patients with CP of unknown etiology. The present study was carried out in 20 families with one family member affected with idiopathic CP. Chromosomal microarray and exome sequencing techniques were performed in all patients. Chromosomal microarray analysis did not show any pathological or probable pathological structural variant. However, the next-generation sequencing study showed a high diagnostic yield. We report 11/20 patients (55%) with different pathogenic or potentially pathogenic variants detected by exome sequencing analysis: five patients with mutations in genes related to hereditary spastic paraplegia, two with mutations in genes related to Aicardi-Goutières syndrome, three with mutations in genes related to developmental/epileptic encephalopathies, and one with a mutation in the PGK1 gene. The accurate and precise patients' selection, the use of a high-throughput genetic platform, the selection of adequate target genes, and the application of rigorous criteria for the clinical interpretation are the most important elements for a good diagnostic performance. Based on our findings, next-generation sequencing should be considered in patients with cryptogenic CP as the first line of genetic workup. IMPACT: Sequencing techniques in CP of uncertain etiology provides a diagnostic yield of 55%. The appropriate selection of cases optimizes the diagnostic yield. NGS facilitate better understanding of new phenotypes of certain genetic diseases.
脑性瘫痪（CP）是一种异质性神经发育障碍，可导致运动和姿势残疾。最近的研究聚焦于病因不明的CP患者的基因诊断。本研究在20个有一名家庭成员患特发性CP的家庭中开展。对所有患者进行了染色体微阵列和外显子组测序技术检测。染色体微阵列分析未显示任何病理性或可能的病理性结构变异。然而，下一代测序研究显示诊断率较高。我们报告，通过外显子组测序分析在11/20例患者（55%）中检测到不同的致病性或潜在致病性变异：5例患者存在与遗传性痉挛性截瘫相关基因的突变，2例存在与Aicardi-Goutières综合征相关基因的突变，3例存在与发育性/癫痫性脑病相关基因的突变，1例存在PGK1基因的突变。准确且精确地选择患者、使用高通量基因平台、选择合适的靶基因以及应用严格的临床解释标准是获得良好诊断效果的最重要因素。基于我们的研究结果，对于隐源性CP患者，应将下一代测序作为基因检查的一线方法。影响：病因不明的CP患者的测序技术诊断率为55%。恰当选择病例可优化诊断率。二代测序有助于更好地理解某些遗传疾病的新表型。
