Chromosomal microarray analysis in clinical evaluation of neurodevelopmental disorders-reporting a novel deletion of SETDB1 and illustration of counseling challenge.
Chromosomal microarray analysis in clinical evaluation of neurodevelopmental disorders-reporting a novel deletion of SETDB1 and illustration of counseling challenge.
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染色体微阵列分析在神经发育障碍临床评估中的应用——报告SETDB1的新缺失并说明咨询挑战
DOI：
10.1038/pr.2016.101
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发表时间：
2016-09
影响因子：
3.6
通讯作者：
Jiang YH
中科院分区：
文献类型：
--
作者：
Xu Q;Goldstein J;Wang P;Gadi IK;Labreche H;Rehder C;Wang WP;McConkie A;Xu X;Jiang YH
背景：研究文献支持拷贝数变异（CNV）在神经发育障碍中的致病性。然而，很少有研究评估的效用和咨询的clinic.Methods：我们分析了CNV研究的结果，从一个队列的遗传学评估自闭症谱系障碍（ASD），发育障碍（DD），智力残疾（ID.Results：22 CNV的21 115先证者被认为是致病的（18.3%）。5个CNV可能是致病性的，22个CNV是未知意义的变体（VUS）。我们发现了7例患有两种以上CNV的病例，2例患有22 q13复杂重排的病例。3. McDermid综合征区。我们确定了一个新的和从头1q21。结论：CNV分析在孤独症遗传学诊断中具有重要价值。然而，由于CNV的变异率和多向表达性，其临床意义的解释和咨询家庭仍然具有挑战性。此外，还鉴定了1q21. 3缺失包括SETDB1提供了进一步的支持，染色质修饰剂在ASD的病因学的作用。
Background:The pathogenicity of copy number variations (CNV) in neurodevelopmental disorders is supported by research literature. However, few studies have evaluated the utility and counseling challenges of CNV analysis in clinic.Methods:We analyzed the findings of CNV studies from a cohort referred for genetics evaluation of autism spectrum disorders (ASD), developmental disability (DD), and intellectual disability (ID).Results:Twenty-two CNV in 21 out of 115 probands are considered to be pathogenic (18.3%). Five CNV are likely pathogenic and 22 CNV are variants of unknown significance (VUS). We have found seven cases with more than two CNV and two with a complex rearrangement of the 22q13. 3 Phelan-McDermid syndrome region. We identified a new and de novo 1q21. 3 deletion that encompasses SETDB1, a gene encoding methylates histone H3 on lysine-9 (H3K9) methyltransferase, in a case with ASD.Conclusion:We provide evidence to support the value of CNV analysis in etiological evaluation of neurodevelopmental disorders in autism genetics clinic. However, interpretation of the clinical significance and counseling families are still challenging because of the variable penetrance and pleotropic expressivity of CNV. In addition, the identification of a 1q21. 3 deletion encompassing SETDB1 provides further support for the role of chromatin modifiers in the etiology of ASD.