title: Exome Sequencing and Linkage Analysis Identified Novel Candidate Genes in Recessive Intellectual Disability Associated with Ataxia.
abstract: BACKGROUND
  Intellectual disability (ID) is a neuro-developmental disorder which causes considerable socio-economic problems. Some ID individuals are also affected by ataxia, and the condition includes different mutations affecting several genes.
  
  
  METHODS
  We used whole exome sequencing (WES) in combination with homozygosity mapping (HM) to identify the genetic defects in five consanguineous families among our cohort study, with two affected children with ID and ataxia as major clinical symptoms.
  
  
  RESULTS
  We identified three novel candidate genes, RIPPLY1, MRPL10, SNX14, and a new mutation in known gene SURF1. All are autosomal genes, except RIPPLY1, which is located on the X chromosome. Two are housekeeping genes, implicated in transcription and translation regulation and intracellular trafficking, and two encode mitochondrial proteins. The pathogenesis of these variants was evaluated by mutation classification, bioinformatic methods, review of medical and biological relevance, co-segregation studies in the particular family, and a normal population study.
  
  
  CONCLUSIONS
  Linkage analysis and exome sequencing of a small number of affected family members is a powerful new technique which can be used to decrease the number of candidate genes in heterogenic disorders such as ID, and may even identify the responsible gene(s).
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Roshanak
authors.initials: R
authors.lastname: Jazayeri
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Fattahi
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Luciana
authors.initials: L
authors.lastname: Musante
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Seyedeh Sedigheh
authors.initials: SS
authors.lastname: Abedini
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Hosseini
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.affiliation: Department of Human Molecular Genetics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Hans Hilger
authors.initials: HH
authors.lastname: Ropers
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
authors.affiliation: Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Kimia
authors.initials: K
authors.lastname: Kahrizi
mesh_terms: D000293:Adolescent; D000328:Adult; D001259:Ataxia / Q000150:complications*; D015331:Cohort Studies; D003241:Consanguinity; D059472:Exome / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics; D012269:Ribosomal Proteins / Q000235:genetics; D058305:Sorting Nexins / Q000235:genetics*; D055815:Young Adult
chemical_list: C000609480:MRPL10 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; C000609481:RIPPLY1 protein, human; D012097:Repressor Proteins; D012269:Ribosomal Proteins; C000594709:SNX14 protein, human; D058305:Sorting Nexins; C092928:Surf-1 protein