@article{eb275cee181043a3a5131375c694743d,
title = "The utility of whole exome sequencing in diagnosing neurological disorders in adults from a highly consanguineous population",
abstract = "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.",
keywords = "APOPT1, KCNJ10, MEM70, MFN2, NSUN2, OPA1, PNKP, SLC12A6, Whole exome sequencing, consanguinity",
author = "Weiyi Mu and Nicoline Schiess and Orthmann-Murphy, {Jennifer L.} and El-Hattab, {Ayman W.}",
note = "Funding Information: Retrospective chart review was performed on 24 adults with undiagnosed neurologic disorders who were evaluated at genetics and neurology clinics at Tawam Hospital in Al Ain, United Arab Emirates between 2014 and 2016 and had WES testing. Data regarding clinical symptoms, neuroimaging results, family history, and genetic testing results were collected. Consanguinity was noted if the individual{\textquoteright}s parents were second cousins or closer in relation. All patients underwent trio WES if parents were available, and proband-only WES if parents were unavailable, by accredited commercial laboratories in Europe or the United States, namely Baylor Genetics Laboratories in Houston, TX; Prevention Genetics in Marshfield, WI; and Centogene in Rostock, Germany. Potentially causative variants underwent Sanger confirmation, and were classified by the laboratory according to the 2015 American College of Medical Genetics guidelines (Richards et al., 2015). Patients were consented for primary and secondary variants, as recommended by ACMG guidelines (Kalia et al., 2017), identified from WES by the clinical genetics team. If clinically indicated, follow-up familial segregation was performed; this included parental testing to determine if two variants in the same recessive gene were biallelic or confirming segregation of likely pathogenic variants in affected siblings. Each of the WES cases were deemed “positive” if a likely disease-causing variant was identified and “negative” if no causative variants were identified. This study was approved by the Al-Ain Medical District Human Research Ethics Committee. Funding Information: The authors thank the Exome Aggregation Consortium and the Genome Aggregation Database, and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about and http://gnomad.broadinstitute.org/about. Publisher Copyright: {\textcopyright} 2019, {\textcopyright} 2019 Informa UK Limited, trading as Taylor & Francis Group.",
year = "2019",
month = jan,
day = "2",
doi = "10.1080/01677063.2018.1555249",
language = "English (US)",
volume = "33",
pages = "21--26",
journal = "Journal of Neurogenetics",
issn = "0167-7063",
publisher = "Informa Healthcare",
number = "1",
}