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首页> 外文期刊>The Application of Clinical Genetics >Utility of trio-based exome sequencing in the elucidation of the genetic basis of isolated syndromic intellectual disability: illustrative cases
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Utility of trio-based exome sequencing in the elucidation of the genetic basis of isolated syndromic intellectual disability: illustrative cases

机译：基于三重基因的外显子组测序在阐明孤立的综合症智障的遗传基础中的实用性：示例

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Introduction: Exome sequencing is recognized as a powerful tool for identifying the genetic cause of intellectual disability (ID). It is uncertain, however, whether only the exome of the proband should be sequenced or if the sequencing of parental genomes is also required, and the resulting increase in diagnostic yield justifies the increase in costs. Patients and methods: We sequenced the exomes of eight individuals with sporadic syndromic ID and their parents. Results and discussion: Likely pathogenic variants were detected in eight candidate genes, namely homozygous or compound heterozygous variants in three autosomal genes ( ADAMTSL2 , NALCN , VPS13B ), one in an X-linked gene ( MID1 ), and de novo heterozygous variants in four autosomal genes ( RYR2 , GABBR2 , CDK13 , DDX3X ). Two patients harbored rare variants in two or more candidate genes, while in three other patients no candidate was identified. In five probands (62%), the detected variants explained their clinical findings. The causative recessive variants would have led to diagnosis even without parental exome sequencing, but for the heterozygous dominant ones, the exome trio-based approach was fundamental in the identification of the de novo likely pathogenic variants.
机译：简介：外显子组测序被认为是识别智力障碍（ID）遗传原因的有力工具。但是，不确定是否仅应该对先证者的外显子组进行测序，还是也需要对亲本基因组进行测序，并且由此产生的诊断产量的增加证明成本的增加是合理的。患者和方法：我们对具有散发性综合征ID的八位个体及其父母的外显子组进行了测序。结果与讨论：在八个候选基因中可能检测到致病性变异，即三个常染色体基因（ADAMTSL2，NALCN，VPS13B），一个X连锁基因（MID1）中的纯合或复合杂合变异，四个新基因中的de novo杂合变异。常染色体基因（RYR2，GABBR2，CDK13，DDX3X）。两名患者在两个或多个候选基因中藏有罕见变异，而在其他三名患者中未鉴定出候选者。在五个先证者（62％）中，检测到的变异体解释了其临床发现。即使没有父母外显子组测序，病原性隐性变异体也将导致诊断，但对于杂合优势显性变异体，基于外显子组三重性的方法是从头确定可能的病原体变异体的基础。

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