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首页> 外文期刊>BMC Medical Genomics >Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly
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Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly

机译：全外显子测序是在智力障碍和小头畸形患者中进行病因诊断的有效方法

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Background Clinical and genetic heterogeneity in monogenetic disorders represents a major diagnostic challenge. Although the presence of particular clinical features may aid in identifying a specific cause in some cases, the majority of patients remain undiagnosed. Here, we investigated the utility of whole-exome sequencing as a diagnostic approach for establishing a molecular diagnosis in a highly heterogeneous group of patients with varied intellectual disability and microcephaly. Methods Whole-exome sequencing was performed in 38 patients, including three sib-pairs, in addition to or in parallel with genetic analyses that were performed during the diagnostic work-up of the study participants. Results In ten out of these 35 families (29?%), we found mutations in genes already known to be related to a disorder in which microcephaly is a main feature. Two unrelated patients had mutations in the ASPM gene. In seven other patients we found mutations in RAB3GAP1 , RNASEH2B, KIF11 , ERCC8 , CASK , DYRK1A and BRCA2 . In one of the sib-pairs, mutations were found in the RTTN gene. Mutations were present in seven out of our ten families with an established etiological diagnosis with recessive inheritance. Conclusions We demonstrate that whole-exome sequencing is a powerful tool for the diagnostic evaluation of patients with highly heterogeneous neurodevelopmental disorders such as intellectual disability with microcephaly. Our results confirm that autosomal recessive disorders are highly prevalent among patients with microcephaly.
机译：背景技术单基因疾病的临床和遗传异质性代表了主要的诊断挑战。尽管在某些情况下特定临床特征的存在可能有助于识别特定原因，但大多数患者仍未得到诊断。在这里，我们调查了全外显子测序作为一种诊断方法的实用性，该方法用于在具有高度智力异质性和小头畸形的高度异类患者中建立分子诊断。方法对38例患者进行全外显子测序，包括3对同胞对，在研究参与者的诊断工作期间进行的遗传分析之外或与之并行进行。结果在这35个家族中的10个（占29％）中，我们发现了已知与小头畸形为主要特征的疾病相关的基因突变。两名无关患者的ASPM基因突变。在另外七名患者中，我们发现RAB3GAP1，RNASEH2B，KIF11，ERCC8，CASK，DYRK1A和BRCA2发生了突变。在其中一个同胞对中，在RTTN基因中发现了突变。在我们的十个家庭中，有七个存在突变，并且病因学诊断为隐性遗传。结论我们证明，全外显子测序是诊断高度异质性神经发育障碍（如小头畸形智力障碍）患者的有力工具。我们的结果证实常染色体隐性遗传疾病在小头畸形患者中非常普遍。

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