Clinical whole genome sequencing as a first-tier test at a resource-limited dysmorphology clinic in Mexico
Clinical whole genome sequencing as a first-tier test at a resource-limited dysmorphology clinic in Mexico
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DOI：
10.1038/s41525-018-0076-1
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发表时间：
2019-02-14
影响因子：
5.3
通讯作者：
Schmidt, Sarah
中科院分区：
文献类型：
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作者：
Scocchia, Alicia;Wigby, Kristen M.;Schmidt, Sarah
患有罕见、未确诊或遗传性疾病（RUGD）的患者通常要经历数年的连续检测，通常被称为“诊断奥德赛”。资源有限地区的患者面临更大的挑战——由于难以获得临床医生、适当的专家和诊断检测，可能永远无法获得明确的诊断。在这里，我们报告了Illumina iHope项目与加利福尼亚儿童基金会和加州婴儿医院的合作，使临床全基因组测序（cWGS）能够在墨西哥北部资源有限的畸形诊所中作为一级测试。对60名疑似遗传诊断且经专家检查临床未解决的先知者进行cWGS检测，并由订购的临床医生完成一项半结构化调查，以调查cWGS结果导致的临床管理变化。在68.3% （n = 41）先证者中鉴定出具有临床意义的基因组发现。无复发分子诊断。拷贝数变异或总体染色体异常占确诊病例的48.8% (n = 20)，包括马赛克三体和疑似衍生染色体。临床管理的定性评估显示，尽管资源有限，但48.8% （n = 20）的诊断患者根据其cWGS结果改变了临床病程。这些数据表明，cWGS一级检测方法可以使疑似遗传疾病的患者受益。
Patients with rare, undiagnosed, or genetic disease (RUGD) often undergo years of serial testing, commonly referred to as the "diagnostic odyssey". Patients in resource-limited areas face even greater challenges-a definitive diagnosis may never be reached due to difficulties in gaining access to clinicians, appropriate specialists, and diagnostic testing. Here, we report on a collaboration of the Illumina iHope Program with the Foundation for the Children of the Californias and Hospital Infantil de Las Californias, to enable deployment of clinical whole genome sequencing (cWGS) as first-tier test in a resource-limited dysmorphology clinic in northern Mexico. A total of 60 probands who were followed for a suspected genetic diagnosis and clinically unresolved after expert examination were tested with cWGS, and the ordering clinicians completed a semi-structured survey to investigate change in clinical management resulting from cWGS findings. Clinically significant genomic findings were identified in 68.3% (n = 41) of probands. No recurrent molecular diagnoses were observed. Copy number variants or gross chromosomal abnormalities accounted for 48.8% (n = 20) of the diagnosed cases, including a mosaic trisomy and suspected derivative chromosomes. A qualitative assessment of clinical management revealed 48.8% (n = 20) of those diagnosed had a change in clinical course based on their cWGS results, despite resource limitations. These data suggest that a cWGS first-tier testing approach can benefit patients with suspected genetic disorders.