title: Etiological yield of SNP microarrays in idiopathic intellectual disability.
abstract: Intellectual disability (ID) has a prevalence of 3% and is classified according to its severity. An underlying etiology cannot be determined in 75-80% in mild ID, and in 20-50% of severe ID. After it has been shown that copy number variations involving short DNA segments may cause ID, genome-wide SNP microarrays are being used as a tool for detecting submicroscopic copy number changes and uniparental disomy. This study was performed to investigate the presence of copy number changes in patients with ID of unidentified etiology. Affymetrix(®) 6.0 SNP microarray platform was used for analysis of 100 patients and their healthy parents, and data were evaluated using various databases and literature. Etiological diagnoses were made in 12 patients (12%). Homozygous deletion in NRXN1 gene and duplication in IL1RAPL1 gene were detected for the first time. Two separate patients had deletions in FOXP2 and UBE2A genes, respectively, for which only few patients have recently been reported. Interstitial and subtelomeric copy number changes were described in 6 patients, in whom routine cytogenetic tools revealed normal results. In one patient uniparental disomy type of Angelman syndrome was diagnosed. SNP microarrays constitute a screening test able to detect very small genomic changes, with a high etiological yield even in patients already evaluated using traditional cytogenetic tools, offer analysis for uniparental disomy and homozygosity, and thereby are helpful in finding novel disease-causing genes: for these reasons they should be considered as a first-tier genetic screening test in the evaluation of patients with ID and autism.
authors: Hacettepe University, Department of Pediatrics, Ankara, Turkey; Hacettepe University, Department of Pediatric Genetics, Ankara, Turkey. Electronic address: geutine@hacettepe.edu.tr.
authors: G Eda
authors: GE
authors: Utine
authors: Hacettepe University, Department of Pediatrics, Ankara, Turkey; Hacettepe University, Department of Pediatric Neurology, Ankara, Turkey.
authors: Göknur
authors: G
authors: Haliloğlu
authors: Hacettepe University, Department of Pediatrics, Ankara, Turkey; Hacettepe University, Department of Pediatric Genetics, Ankara, Turkey.
authors: Bilge
authors: B
authors: Volkan-Salancı
authors: Hacettepe University, Department of Pediatric Genetics, Ankara, Turkey; Hacettepe University, Department of Medical Genetics, Ankara, Turkey.
authors: Arda
authors: A
authors: Çetinkaya
authors: Hacettepe University, Department of Pediatrics, Ankara, Turkey; Hacettepe University, Department of Pediatric Genetics, Ankara, Turkey.
authors: Pelin Ö
authors: PÖ
authors: Kiper
authors: Hacettepe University, Department of Pediatrics, Ankara, Turkey; Hacettepe University, Department of Pediatric Genetics, Ankara, Turkey.
authors: Yasemin
authors: Y
authors: Alanay
authors: Hacettepe University, Department of Pediatric Genetics, Ankara, Turkey; Hacettepe University, Department of Medical Genetics, Ankara, Turkey.
authors: Dilek
authors: D
authors: Aktaş
authors: Hacettepe University, Department of Pediatrics, Ankara, Turkey; Hacettepe University, Department of Pediatric Neurology, Ankara, Turkey.
authors: Banu
authors: B
authors: Anlar
authors: Hacettepe University, Department of Pediatrics, Ankara, Turkey; Hacettepe University, Department of Pediatric Neurology, Ankara, Turkey.
authors: Meral
authors: M
authors: Topçu
authors: Hacettepe University, Department of Pediatrics, Ankara, Turkey; Hacettepe University, Department of Pediatric Genetics, Ankara, Turkey.
authors: Koray
authors: K
authors: Boduroğlu
authors: Hacettepe University, Department of Pediatric Genetics, Ankara, Turkey; Hacettepe University, Department of Medical Genetics, Ankara, Turkey.
authors: Mehmet
authors: M
authors: Alikaşifoğlu
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000209:etiology* / Q000235:genetics; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D046228:Microarray Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D024182:Uniparental Disomy / Q000209:etiology* / Q000235:genetics; D055815:Young Adult
keywords: FOXP2; Intellectual disability; NRXN1; SNP microarray; Subtelomeric rearrangements; UBE2A; Uniparental disomy