title: Exome sequencing and diffusion tensor imaging in developmental disabilities.
abstract: BACKGROUND
  We had previously shown that arcuate fasciculus is poorly developed in patients with intellectual and developmental disabilities (IDD) using diffusion tensor imaging (DTI). In the present study, we used exome sequencing to identify the candidate variants in IDD patients with and without DTI abnormalities.
  
  
  METHODS
  Eighteen children with IDD (age: 67 ± 36 mo, 9 females) were included in the present study. The DTI was used to determine the integrity of arcuate fasciculus. The next-generation sequencing was performed on the Solid 4 platform. A novel, analytical strategy was developed to identify a set of candidate genes of interest. We then searched for novel, nonsynonymous variants in the patients within this subset of genes and in known IDD genes.
  
  
  RESULTS
  Seven novel, nonsynonymous (all of them were heterozygous, missense) variants belonged to ultraconserved genes that are known to cause abnormal brain morphology in mutant mice. Similarly, three novel, nonsynonymous (all of them were heterozygous, missense) variants belonged to known IDD genes. Two patients with underdeveloped arcuate fasciculus had novel, nonsynonymous variants in genes (MID1 and EN2) regulating axon guidance pathway.
  
  
  CONCLUSIONS
  Exome sequencing identified several new genetic causes of IDD.
authors: 1] Department of Pediatrics, Wayne State University, Detroit, Michigan [2] Department of Neurology, Wayne State University, Detroit, Michigan [3] PET Center, Children's Hospital of Michigan, Detroit Medical Center, Detroit, Michigan.
authors: Senthil
authors: S
authors: Sundaram
authors: 1] Department of Pediatrics, Wayne State University, Detroit, Michigan [2] Department of Neurology, Wayne State University, Detroit, Michigan.
authors: A H M
authors: AH
authors: Huq
authors: 1] Department of Pediatrics, Wayne State University, Detroit, Michigan [2] Department of Neurology, Wayne State University, Detroit, Michigan.
authors: Tammy
authors: T
authors: Hsia
authors: 1] Department of Pediatrics, Wayne State University, Detroit, Michigan [2] Department of Neurology, Wayne State University, Detroit, Michigan [3] PET Center, Children's Hospital of Michigan, Detroit Medical Center, Detroit, Michigan.
authors: Harry
authors: H
authors: Chugani
mesh_terms: D001483:Base Sequence; D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000235:genetics*; D056324:Diffusion Tensor Imaging / Q000379:methods*; D059472:Exome / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008868:Microtubule Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics; D044767:Ubiquitin-Protein Ligases; D000099266:Engrailed 2 Protein
chemical_list: D018398:Homeodomain Proteins; D008868:Microtubule Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D000099266:Engrailed 2 Protein; C109052:MID1 protein, human