Clinical exome sequencing: results from 2819 samples reflecting 1000 families.
Clinical exome sequencing: results from 2819 samples reflecting 1000 families.
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临床外显子组测序：2819个样品的结果反映了1000个家庭。
DOI：
10.1038/ejhg.2016.146
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发表时间：
2017-02
期刊：
影响因子：
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通讯作者：
Abou Jamra R
中科院分区：
文献类型：
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作者：
Trujillano D;Bertoli-Avella AM;Kumar Kandaswamy K;Weiss ME;Köster J;Marais A;Paknia O;Schröder R;Garcia-Aznar JM;Werber M;Brandau O;Calvo Del Castillo M;Baldi C;Wessel K;Kishore S;Nahavandi N;Eyaid W;Al Rifai MT;Al-Rumayyan A;Al-Twaijri W;Alothaim A;Alhashem A;Al-Sannaa N;Al-Balwi M;Alfadhel M;Rolfs A;Abou Jamra R
我们报告了1000个诊断性WES病例的结果，这些病例基于来自54个国家的2819个测序样本，具有广泛的表型谱。将请求医生提供的临床信息翻译为HPO术语。根据标准化设置进行WES过程。我们在307个家庭（30.7%）中确定了潜在的致病性或可能的致病性变异。在另外253个家庭（25.3%）的变异未知的意义，可能解释索引患者的临床症状被确定。WES能够及时诊断遗传性疾病，验证PTPN 23，KCTD 3，SCN 3A，PPOX，FRMPD 4和SCN 1B的特定遗传性疾病的因果关系，并通过检测同一患者不同基因中的两种致病变体来设置双重诊断。我们观察到一个更好的诊断率在血缘关系的家庭，在严重和综合征的表型。我们的研究结果表明，WES有一个更好的收益率在患者中，目前有几个症状，而不是一个孤立的异常。我们还验证了WES作为一种有效的诊断工具的临床益处，特别是在非特异性或异质性表型中。我们建议在没有明确鉴别诊断的情况下，将WES作为所有病例的一线诊断，以方便个人医疗护理。
We report our results of 1000 diagnostic WES cases based on 2819 sequenced samples from 54 countries with a wide phenotypic spectrum. Clinical information given by the requesting physicians was translated to HPO terms. WES processes were performed according to standardized settings. We identified the underlying pathogenic or likely pathogenic variants in 307 families (30.7%). In further 253 families (25.3%) a variant of unknown significance, possibly explaining the clinical symptoms of the index patient was identified. WES enabled timely diagnosing of genetic diseases, validation of causality of specific genetic disorders of PTPN23, KCTD3, SCN3A, PPOX, FRMPD4, and SCN1B, and setting dual diagnoses by detecting two causative variants in distinct genes in the same patient. We observed a better diagnostic yield in consanguineous families, in severe and in syndromic phenotypes. Our results suggest that WES has a better yield in patients that present with several symptoms, rather than an isolated abnormality. We also validate the clinical benefit of WES as an effective diagnostic tool, particularly in nonspecific or heterogeneous phenotypes. We recommend WES as a first-line diagnostic in all cases without a clear differential diagnosis, to facilitate personal medical care.