Mu Weiyi, Schiess Nicoline, Orthmann-Murphy Jennifer L, El-Hattab Ayman W
a Institute of Genetic Medicine , Johns Hopkins University , Baltimore , MD , USA.
b Department of Neurology , Johns Hopkins University , Baltimore , MD , USA.
J Neurogenet. 2019 Mar;33(1):21-26. doi: 10.1080/01677063.2018.1555249. Epub 2019 Feb 6.
There is increasing evidence that whole exome sequencing (WES) has a high diagnostic yield and is cost-efficient for individuals with neurological phenotypes. However, there is limited data on the use of WES in non-Western populations, including populations with a high rate of consanguinity. Retrospective chart review was performed on 24 adults with undiagnosed neurological symptoms evaluated in genetics and neurology clinics in a tertiary care facility on the Arabian Peninsula, and had WES between 2014 and 2016. Definitive diagnoses were made in 13/24 (54%) of cases. Of these, 5/13 (38%) revealed novel pathogenic variants. Of the known 19/24 (79%) consanguineous cases, diagnostic rate was slightly higher, 11/19 (58%) as compared to 2/5 (40%) among non-consanguineous cases. Autosomal recessive disorders comprised 10/13 (77%) of molecular diagnoses, all found to be due to homozygous pathogenic variants among consanguineous cases. WES in this cohort of adults with neurological symptoms had a high diagnostic rate likely due to high consanguinity rates in this population, as evidenced by the high diagnostic rate of homozygous pathogenic variants.
越来越多的证据表明，对于具有神经学表型的个体，全外显子组测序（WES）具有很高的诊断率且成本效益高。然而，关于WES在非西方人群（包括近亲结婚率高的人群）中的应用数据有限。对阿拉伯半岛一家三级医疗机构的遗传学和神经学诊所评估的24名有未确诊神经症状的成年人进行了回顾性病历审查，这些人在2014年至2016年间进行了WES检测。13/24（54%）的病例做出了明确诊断。其中，5/13（38%）发现了新的致病变异。在已知的19/24（79%）近亲结婚病例中，诊断率略高，为11/19（58%），而非近亲结婚病例中为2/5（40%）。常染色体隐性疾病占分子诊断的10/13（77%），所有这些都被发现是由于近亲结婚病例中的纯合致病变异。在这一有神经症状的成年人群体中，WES具有很高的诊断率，这可能是由于该人群中近亲结婚率高，纯合致病变异的高诊断率证明了这一点。
