title: The genetics of nonsyndromic bilateral Duane retraction syndrome.
abstract: To assess the importance of monogenic mutations and chromosomal copy number variants (CNVs) in the occurrence of nonsyndromic bilateral Duane retraction syndrome (bilateral nsDRS).
  
  
  
  The medical records of 12 patients with bilateral nsDRS were reviewed. Genes associated with DRS and associated congenital cranial dysinnervation disorders (SALL4, CHN1, HOXA1, TUBB3, and KIF21A) were sequenced in the standard fashion in each patient. Array comparative genomic hybridization (array CGH) was performed using Affymetrix Cytogenetics Whole-Genome 2.7M array, and the results were analyzed using Affymetrix Chromosome Analysis Suite v1.2. CNVs were assessed as unlikely to be pathologic if they were also present in the Database of Genomic Variants (DGV) or our local database of array CGH results in 150 normal individuals of Middle Eastern ethnicity.
  
  
  
  No patient had a sequence mutation in SALL4, CHN1, HOXA1, TUBB3, or KIF21A. These 12 patients each had 36-42 chromosomal deletions and/or duplications (mean with standard deviation, 26.25 ± 6.77), but all of these CNVs were present either in the DGV or in our local database of normal individuals of similar ethnicity and, therefore, are considered nonpathogenic.
  
  
  
  The results reported here suggest that bilateral nsDRS is not usually associated with mutations in these genes or with chromosomal CNVs. Current evidence suggests other factors such as epigenetic and/or teratogenic abnormalities may be a potential cause of bilateral nsDRS.
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia; Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, United Arab Emirates. Electronic address: abuamero@gmail.com.
authors.forename: Khaled K
authors.initials: KK
authors.lastname: Abu-Amero
authors.affiliation: Eye Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.
authors.forename: Arif O
authors.initials: AO
authors.lastname: Khan
authors.affiliation: IWK Health Centre Eye Care Team, Halifax, Nova Scotia, Canada.
authors.forename: Darren T
authors.initials: DT
authors.lastname: Oystreck
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Altaf A
authors.initials: AA
authors.lastname: Kondkar
authors.affiliation: Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Bosley
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics*; D058674:Chromosome Duplication; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D004370:Duane Retraction Syndrome / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D055815:Young Adult