PDF(Pubmed)
Abstract：
BACKGROUND: Aneuploids, copy number variations (CNVs), and single nucleotide variants in specific genes are the main genetic causes of developmental delay (DD) and intellectual disability disorder (IDD). These genetic changes can be detected using chromosome analysis, chromosomal microarray (CMA), and next-generation DNA sequencing techniques. Therefore; In this study, we aimed to investigate the importance of CMA in determining the genomic etiology of unexplained DD and IDD in 123 patients.
METHODS: For 123 patients, chromosome analysis, DNA fragment analysis and microarray were performed. Conventional G-band karyotype analysis from peripheral blood was performed as part of the initial screening tests. FMR1 gene CGG repeat number and methylation analysis were carried out to exclude fragile X syndrome.
RESULTS: CMA analysis was performed in 123 unexplained IDD/DD patients with normal karyotypes and fragile X screening, which were evaluated by conventional cytogenetics. Forty-four CNVs were detected in 39 (39/123=31.7%) patients. Twelve CNV variant of unknown significance (VUS) (9.75%) patients and 7 CNV benign (5.69%) patients were reported. In 6 patients, one or more pathogenic CNVs were determined. Therefore, the diagnostic efficiency of CMA was found to be 31.7% (39/123).
CONCLUSIONS: Today, genetic analysis is still not part of the routine in the evaluation of IDD patients who present to psychiatry clinics. A genetic diagnosis from CMA can eliminate genetic question marks and thus alter the clinical management of patients. Approximately one-third of the positive CMA findings are clinically intervenable. However, the emergence of CNVs as important risk factors for multiple disorders increases the need for individuals with comorbid neurodevelopmental conditions to be the priority where the CMA test is recommended.
METHODS: For 123 patients, chromosome analysis, DNA fragment analysis and microarray were performed. Conventional G-band karyotype analysis from peripheral blood was performed as part of the initial screening tests. FMR1 gene CGG repeat number and methylation analysis were carried out to exclude fragile X syndrome.
RESULTS: CMA analysis was performed in 123 unexplained IDD/DD patients with normal karyotypes and fragile X screening, which were evaluated by conventional cytogenetics. Forty-four CNVs were detected in 39 (39/123=31.7%) patients. Twelve CNV variant of unknown significance (VUS) (9.75%) patients and 7 CNV benign (5.69%) patients were reported. In 6 patients, one or more pathogenic CNVs were determined. Therefore, the diagnostic efficiency of CMA was found to be 31.7% (39/123).
CONCLUSIONS: Today, genetic analysis is still not part of the routine in the evaluation of IDD patients who present to psychiatry clinics. A genetic diagnosis from CMA can eliminate genetic question marks and thus alter the clinical management of patients. Approximately one-third of the positive CMA findings are clinically intervenable. However, the emergence of CNVs as important risk factors for multiple disorders increases the need for individuals with comorbid neurodevelopmental conditions to be the priority where the CMA test is recommended.
摘要：
背景：非整倍体，拷贝数变化(CNVs)，而特定基因中的单核苷酸变异是导致发育迟缓(DD)和智力障碍(IDD)的主要遗传原因。这些遗传变化可以通过染色体分析来检测,染色体微阵列（CMA），和下一代DNA测序技术。因此；在这项研究中，我们旨在研究CMA在确定123例原因不明的DD和IDD的基因组病因中的重要性.
方法：对于123例患者，染色体分析,进行DNA片段分析和微阵列。作为初始筛选测试的一部分，进行了来自外周血的常规G带核型分析。进行FMR1基因CGG重复序列数和甲基化分析以排除脆性X综合征。
结果：对123例原因不明的IDD/DD患者进行了CMA分析，这些患者具有正常核型和脆性X筛查，通过常规细胞遗传学进行评估。在39例(39/123=31.7%)患者中检测到44例CNV。报告了12例意义不明的CNV变异（VUS）（9.75％）患者和7例CNV良性（5.69％）患者。在6名患者中，确定一种或多种致病性CNV。因此,CMA的诊断效率为31.7%(39/123).
结论：今天，遗传分析仍然不是评估出现在精神科诊所的IDD患者的常规的一部分.CMA的遗传诊断可以消除遗传问号，从而改变患者的临床管理。大约三分之一的CMA阳性发现是临床可干预的。然而,CNVs作为多种疾病的重要危险因素的出现,增加了对患有共病神经发育疾病的个体的需要,在推荐CMA检测的情况下优先考虑这些个体.
方法：对于123例患者，染色体分析,进行DNA片段分析和微阵列。作为初始筛选测试的一部分，进行了来自外周血的常规G带核型分析。进行FMR1基因CGG重复序列数和甲基化分析以排除脆性X综合征。
结果：对123例原因不明的IDD/DD患者进行了CMA分析，这些患者具有正常核型和脆性X筛查，通过常规细胞遗传学进行评估。在39例(39/123=31.7%)患者中检测到44例CNV。报告了12例意义不明的CNV变异（VUS）（9.75％）患者和7例CNV良性（5.69％）患者。在6名患者中，确定一种或多种致病性CNV。因此,CMA的诊断效率为31.7%(39/123).
结论：今天，遗传分析仍然不是评估出现在精神科诊所的IDD患者的常规的一部分.CMA的遗传诊断可以消除遗传问号，从而改变患者的临床管理。大约三分之一的CMA阳性发现是临床可干预的。然而,CNVs作为多种疾病的重要危险因素的出现,增加了对患有共病神经发育疾病的个体的需要,在推荐CMA检测的情况下优先考虑这些个体.
