全基因组测序在医学遗传学诊所的成功应用
Successful Application of Whole Genome Sequencing in a Medical Genetics Clinic.
作者信息
Bick David, Fraser Pamela C, Gutzeit Michael F, Harris Jeremy M, Hambuch Tina M, Helbling Daniel C, Jacob Howard J, Kersten Juliet N, Leuthner Steven R, May Thomas, North Paula E, Prisco Sasha Z, Schuler Bryce A, Shimoyama Mary, Strong Kimberly A, Van Why Scott K, Veith Regan, Verbsky James, Weborg Arthur M, Wilk Brandon M, Willoughby Rodney E, Worthey Elizabeth A, Dimmock David P
机构信息
HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, United States.
Aerodigestive and Genomic Services, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, United States.
出版信息
J Pediatr Genet. 2017 Jun;6(2):61-76. doi: 10.1055/s-0036-1593968. Epub 2016 Nov 28.
Abstract
A pilot program was initiated using whole genome sequencing (WGS) to diagnose suspected genetic disorders in the Genetics Clinic at Children's Hospital of Wisconsin. Twenty-two patients underwent WGS between 2010 and 2013. Initially, we obtained a 14% (3/22) diagnosis rate over 2 years; with subsequent reanalysis, this increased to 36% (8/22). Disease causing variants were identified in SKIV2L, CECR1, DGKE, PYCR2, RYR1, PDGFRB, EFTUD2, and BCS1L. In 75% (6/8) of diagnosed cases, the diagnosis affected treatment and/or medical surveillance. Additionally, one case demonstrated a homozygous A18V variant in VLDLR that appears to be associated with a previously undescribed phenotype.
摘要
威斯康星儿童医院遗传门诊启动了一项使用全基因组测序（WGS）诊断疑似遗传疾病的试点项目。2010年至2013年间，22名患者接受了全基因组测序。最初，我们在两年内的诊断率为14%（3/22）；随后经过重新分析，这一比例提高到了36%（8/22）。在SKIV2L、CECR1、DGKE、PYCR2、RYR1、PDGFRB、EFTUD2和BCS1L中鉴定出了致病变异。在75%（6/8）的确诊病例中，诊断结果影响了治疗和/或医疗监测。此外，有一例在VLDLR中显示出纯合的A18V变异，这似乎与一种先前未描述的表型有关。
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