Rosell Allyn McConkie, Pena Loren D M, Schoch Kelly, Spillmann Rebecca, Sullivan Jennifer, Hooper Stephen R, Jiang Yong-Hui, Mathey-Andrews Nicolas, Goldstein David B, Shashi Vandana
Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 103757, Durham, NC, 27710, USA.
Department of Allied Health, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
J Genet Couns. 2016 Oct;25(5):1019-31. doi: 10.1007/s10897-016-9933-1. Epub 2016 Feb 12.
Due to the lack of empirical information on parental perceptions of primary results of whole exome sequencing (WES), we conducted a retrospective semi-structured interview with 19 parents of children who had undergone WES. Perceptions explored during the interview included factors that would contribute to parental empowerment such as: parental expectations, understanding of the WES and results, utilization of the WES information, and communication of findings to health/educational professionals and family members. Results of the WES had previously been communicated to families within a novel framework of clinical diagnostic categories: 5/19 had Definite diagnoses, 6/19 had Likely diagnoses, 3/19 had Possible diagnosis and 5/19 had No diagnosis. All parents interviewed expressed a sense of duty to pursue the WES in search of a diagnosis; however, their expectations were tempered by previous experiences with negative genetic testing results. Approximately half the parents worried that a primary diagnosis that would be lethal might be identified; however, the hope of a diagnosis outweighed this concern. Parents were accurately able to summarize their child's WES findings, understood the implications for recurrence risks, and were able to communicate these findings to family and medical/educational providers. The majority of those with a Definite/Likely diagnosis felt that their child's medical care was more focused, or there was a reduction in worry, despite the lack of a specific treatment. Irrespective of diagnostic outcome, parents recommended that follow-up visits be built into the process. Several parents expressed a desire to have all variants of unknown significance (VUS) reported to them so that they could investigate these themselves. Finally, for some families whose children had a Definite/Likely diagnosis, there was remaining frustration and a sense of isolation, due to the limited information that was available about the diagnosed rare disorders and the inability to connect to other families, suggesting that for families with rare genetic disorders, the diagnostic odyssey does not necessarily end with a diagnosis. Qualitative interviewing served a meaningful role in eliciting new information about parental motivations, expectations, and knowledge of WES. Our findings highlight a need for continued communication with families as we navigate the new landscape of genomic sequencing.
由于缺乏关于父母对全外显子组测序（WES）主要结果认知的实证信息，我们对19位孩子接受过WES的家长进行了回顾性半结构化访谈。访谈中探讨的认知包括有助于增强父母权能的因素，如：父母期望、对WES及结果的理解、WES信息的利用，以及向健康/教育专业人员和家庭成员传达结果。WES的结果此前已在一个新的临床诊断类别框架内传达给家庭：19例中有5例确诊，6例可能确诊，3例可能诊断，5例未诊断。所有接受访谈的家长都表示有责任进行WES以寻求诊断；然而，他们的期望因之前负面基因检测结果的经历而有所缓和。大约一半的家长担心可能会发现致命的初步诊断结果；然而，诊断的希望超过了这种担忧。家长能够准确总结孩子的WES结果，理解复发风险的影响，并能够将这些结果传达给家人以及医疗/教育提供者。大多数确诊/可能确诊的家长认为，尽管缺乏具体治疗方法，但孩子的医疗护理更加有针对性，或者担忧有所减轻。无论诊断结果如何，家长都建议在这个过程中安排随访。几位家长表示希望被告知所有意义未明的变异（VUS），以便他们自己进行研究。最后，对于一些孩子确诊/可能确诊的家庭来说，由于关于所诊断罕见疾病的可用信息有限，且无法与其他家庭建立联系，仍然存在挫折感和孤立感，这表明对于患有罕见遗传疾病的家庭来说，诊断之旅不一定随着诊断而结束。定性访谈在获取关于父母对WES的动机、期望和知识的新信息方面发挥了重要作用。我们的研究结果凸显了在我们探索基因组测序新领域时与家庭持续沟通的必要性。
