Community-based recruitment and exome sequencing indicates high diagnostic yield in adults with intellectual disability.
Community-based recruitment and exome sequencing indicates high diagnostic yield in adults with intellectual disability.
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DOI：
10.1002/mgg3.1439
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发表时间：
2020-10
影响因子：
2
通讯作者：
Gibbs R
中科院分区：
文献类型：
--
作者：
Sabo A;Murdock D;Dugan S;Meng Q;Gingras MC;Hu J;Muzny D;Gibbs R
对智力残疾患者进行基因诊断有利于患者及其家属，因为这可以为预后提供信息，导致适当的治疗，并促进获得医疗和支持性服务。外显子组测序已经成功地应用于诊断环境，但大多数临床外显子组转诊是儿科患者，许多患有ID的成年人缺乏全面的遗传评估。我们独特的招聘策略包括与服务和教育提供商合作，为有身份证的个人提供服务。我们对每个招募的家庭进行了外显子组测序和分析，以及临床变异解释。所有参加研究的五个家庭都选择了返回基因结果。在5个家族中的3个中，外显子组测序分析发现了KANSL1、TUSC3和MED13L基因的致病性或可能致病性变异。家庭讨论了结果和任何潜在的医疗跟进与董事会认证的临床遗传学家预约。我们的研究表明，外显子组测序作为未进行全面测序基因检测的成年ID患者的诊断工具。包括选择通过基因诊所返回结果的研究可以帮助减少儿童和成人ID患者外显子组诊断测试的差异。外显子组测序已经成功地应用于诊断环境，但大多数临床外显子组转诊是儿科患者，许多智力残疾的成年人缺乏全面的遗传评估。我们的研究指出，外显子组测序作为未进行全面测序基因检测的成年患者的诊断工具的高产量。包括选择通过遗传诊所返回结果的研究可以帮助减少儿科和成人患者外显子组诊断测试的差异。
Establishing a genetic diagnosis for individuals with intellectual disability (ID) benefits patients and their families as it may inform the prognosis, lead to appropriate therapy, and facilitate access to medical and supportive services. Exome sequencing has been successfully applied in a diagnostic setting, but most clinical exome referrals are pediatric patients, with many adults with ID lacking a comprehensive genetic evaluation. Our unique recruitment strategy involved partnering with service and education providers for individuals with ID. We performed exome sequencing and analysis, and clinical variant interpretation for each recruited family. All five families enrolled in the study opted‐in for the return of genetic results. In three out of five families exome sequencing analysis identified pathogenic or likely pathogenic variants in KANSL1, TUSC3, and MED13L genes. Families discussed the results and any potential medical follow‐up in an appointment with a board certified clinical geneticist. Our study suggests high yield of exome sequencing as a diagnostic tool in adult patients with ID who have not undergone comprehensive sequencing‐based genetic testing. Research studies including an option of return of results through a genetic clinic could help minimize the disparity in exome diagnostic testing between pediatric and adult patients with ID. Exome sequencing has been successfully applied in a diagnostic setting, but most clinical exome referrals are pediatric patients, with many adults with intellectual disability lacking a comprehensive genetic evaluation. Our study points to high yield of exome sequencing as a diagnostic tool in adult patients who have not undergone comprehensive sequencing‐based genetic testing. Research studies including an option of return of results through a genetic clinic could help minimize the disparity in exome diagnostic testing between pediatric and adult patients.
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影响因子：
3
作者：
Reid JG;Carroll A;Veeraraghavan N;Dahdouli M;Sundquist A;English A;Bainbridge M;White S;Salerno W;Buhay C;Yu F;Muzny D;Daly R;Duyk G;Gibbs RA;Boerwinkle E
通讯作者：
Boerwinkle E
影响因子：
1.9
作者：
Asadollahi, Reza;Zweier, Markus;Rauch, Anita
通讯作者：
Rauch, Anita
影响因子：
2
作者：
Boutry-Kryza, Nadia;Labalme, Audrey;Sanlaville, Damien
通讯作者：
Sanlaville, Damien
影响因子：
9.8
作者：
Garshasbi, Masoud;Hadavi, Valeh;Kuss, Andreas Walter
通讯作者：
Kuss, Andreas Walter
影响因子：
64.8
作者：
Karczewski, Konrad J;Francioli, Laurent C;MacArthur, Daniel G
通讯作者：
MacArthur, Daniel G