Iglesias Alejandro, Anyane-Yeboa Kwame, Wynn Julia, Wilson Ashley, Truitt Cho Megan, Guzman Edwin, Sisson Rebecca, Egan Claire, Chung Wendy K
Division of Clinical Genetics, Department of Pediatrics, Columbia University Medical Center, New York, New York, USA.
Division of Molecular Genetics, Department of Pediatrics, Columbia University Medical Center, New York, New York, USA.
Genet Med. 2014 Dec;16(12):922-31. doi: 10.1038/gim.2014.58. Epub 2014 Jun 5.
Reports of the use of whole-exome sequencing in clinical practice are limited. We report our experience with whole-exome sequencing in 115 patients in a single center and evaluate its feasibility and clinical usefulness in clinical care.
Whole-exome sequencing was utilized based on the judgment of three clinical geneticists. We describe age, gender, ethnicity, consanguinity, indication for testing, family history, insurance, laboratory results, clinician interpretation of results, and impact on patient care.
Most patients were children (78.9%). The most common indications for testing were birth defects (24.3%) and developmental delay (25.2%). We identified four new candidate human disease genes and possibly expanded the disease phenotypes associated with five different genes. Establishing a diagnosis led to discontinuation of additional planned testing in all patients, screening for additional manifestations in eight, altered management in fourteen, novel therapy in two, identification of other familial mutation carriers in five, and reproductive planning in six.
Our results show that whole-exome sequencing is feasible, has clinical usefulness, and allows timely medical interventions, informed reproductive choices, and avoidance of additional testing. Our results also suggest phenotype expansion and identification of new candidate disease genes that would have been impossible to diagnose by other targeted testing methods.
关于临床实践中使用全外显子组测序的报告有限。我们报告了在单一中心对115例患者进行全外显子组测序的经验，并评估其在临床护理中的可行性和临床实用性。
基于三位临床遗传学家的判断使用全外显子组测序。我们描述了患者的年龄、性别、种族、近亲结婚情况、检测指征、家族史、保险情况、实验室结果、临床医生对结果的解读以及对患者护理的影响。
大多数患者为儿童（78.9%）。最常见的检测指征是出生缺陷（24.3%）和发育迟缓（25.2%）。我们鉴定出四个新的人类疾病候选基因，并可能扩展了与五个不同基因相关的疾病表型。确诊后，所有患者均停止了额外的计划检测，八名患者进行了额外表现的筛查，十四名患者改变了治疗方案，两名患者采用了新疗法，五名患者鉴定出了其他家族性突变携带者，六名患者进行了生育规划。
我们的结果表明，全外显子组测序是可行的，具有临床实用性，并能实现及时的医疗干预、明智的生育选择以及避免额外检测。我们的结果还提示了表型扩展以及新的疾病候选基因的鉴定，而这些是其他靶向检测方法无法诊断的。
