title: The clinical utility of molecular karyotyping for neurocognitive phenotypes in a consanguineous population.
abstract: OBJECTIVE
  Molecular karyotyping has rapidly become the test of choice in patients with neurocognitive phenotypes, but studies of its clinical utility have largely been limited to outbred populations. In consanguineous populations, single-gene recessive causes of neurocognitive phenotypes are expected to account for a relatively high percentage of cases, thus diminishing the yield of molecular karyotyping. The aim of this study was to test the clinical yield of molecular karyotyping in the highly consanguineous population of Saudi Arabia.
  
  
  METHODS
  We have reviewed the data of 584 patients with neurocognitive phenotypes (mainly referred from pediatric neurology clinics), all evaluated by a single clinical geneticist.
  
  
  RESULTS
  At least 21% of tested cases had chromosomal aberrations that are likely disease-causing. These changes include both known and novel deletion syndromes. The higher yield of molecular karyotyping in this study as compared with the commonly cited 11% can be explained by our ability to efficiently identify single-gene disorders, thus enriching the samples that underwent molecular karyotyping for de novo chromosomal aberrations. We show that we were able to identify a causal mutation in 37% of cases on a clinical basis with the help of autozygome analysis, thus bypassing the need for molecular karyotyping.
  
  
  CONCLUSIONS
  Our study confirms the clinical utility of molecular karyotyping even in highly consanguineous populations.
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Al-Qattan
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Salma M
authors.initials: SM
authors.lastname: Wakil
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Shamsa
authors.initials: S
authors.lastname: Anazi
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Anas M
authors.initials: AM
authors.lastname: Alazami
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Nisha
authors.initials: N
authors.lastname: Patel
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Ranad
authors.initials: R
authors.lastname: Shaheen
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Hanan E
authors.initials: HE
authors.lastname: Shamseldin
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Samya T
authors.initials: ST
authors.lastname: Hagos
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Haya M
authors.initials: HM
authors.lastname: AlDossari
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mustafa A
authors.initials: MA
authors.lastname: Salih
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia.|Department of Pediatrics, Children Hospital, Ain Shams University, Cairo, Egypt.
authors.forename: Heba Y
authors.initials: HY
authors.lastname: El Khashab
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Amal Y
authors.initials: AY
authors.lastname: Kentab
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammed N
authors.initials: MN
authors.lastname: AlNasser
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Fahad A
authors.initials: FA
authors.lastname: Bashiri
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Namik
authors.initials: N
authors.lastname: Kaya
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Mais O
authors.initials: MO
authors.lastname: Hashem
authors.affiliation: Department of Genetics, Research Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.|Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
authors.forename: Fowzan S
authors.initials: FS
authors.lastname: Alkuraya
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D003241:Consanguinity; D056915:DNA Copy Number Variations; D002658:Developmental Disabilities; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D007621:Karyotyping / Q000379:methods; D008297:Male; D019965:Neurocognitive Disorders / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012529:Saudi Arabia / Q000453:epidemiology; D055815:Young Adult