The utility of whole exome analysis has been extensively demonstrated in research settings, but its clinical utility as a first‐tier genetic test has not been well documented from diagnostic and health economic standpoints in real‐life clinical settings. We performed medical exome analyses focusing on a clinically interpretable portion of the genome (4,813 genes) as a first‐tier genetic test for 360 consecutive patients visiting a genetics clinic at a tertiary children's hospital in Japan, over a 3‐year period. Bioinformatics analyses were conducted using standard software. A molecular diagnosis was made in 171 patients involving a total of 107 causative genes. Among these 107 causative genes, 57 genes were classified as genes with potential organ‐specific interventions and management strategies. Clinically relevant results were obtained in 26% of the total cohort and 54% of the patients with a definitive molecular diagnosis. Performing the medical exome analysis at the time of the initial visit to the tertiary center, rather than after visits to pertinent specialists, brain MRI examination, and G‐banded chromosome testing, would have reduced the financial cost by 197 euros according to retrospective calculation under multiple assumption. The present study demonstrated a high diagnostic yield (47.5%) for singleton medical exome analysis as a first‐tier test in a real‐life setting. Medical exome analysis yielded clinically relevant information in a quarter of the total patient cohort. The application of genomic testing during the initial visit to a tertiary medical center could be a rational approach to the diagnosis of patients with suspected genetic disorders.

中文翻译：

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第三中心的连续医学外显子组分析：诊断和健康经济结果。

整个外显子组分析的效用已在研究环境中得到了充分证明，但从现实生活中的临床诊断和健康经济角度出发，其作为一级基因检测的临床效用尚未得到充分证明。我们进行了医学外显子组分析，重点是基因组的临床可解释部分（4,813个基因），作为对日本三级儿童医院遗传学诊所连续3年访问的360例连续患者的一级遗传测试。使用标准软件进行生物信息学分析。在171名患者中进行了分子诊断，涉及107个致病基因。在这107个致病基因中，有57个基因被归类为具有潜在器官特异性干预和管理策略的基因。在确定的分子诊断中，有26％的患者和54％的患者获得了临床相关的结果。根据以下回顾性计算，在初次访问三级医疗中心时进行医学外显子组分析，而不是先拜访相关专家，进行脑MRI检查和G带染色体检查，可以节省197欧元的财务费用。多重假设。本研究表明，作为单例医学外显子组分析在现实生活中的第一级测试，诊断率很高（47.5％）。医学外显子组分析产生的临床相关信息占患者总数的四分之一。