title: A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability.
abstract: In the context of a comprehensive research project, investigating novel autosomal recessive intellectual disability (ARID) genes, linkage analysis based on autozygosity mapping helped identify an intellectual disability locus on Chr.12q24, in an Iranian family (LOD score = 3.7). Next-generation sequencing (NGS) following exon enrichment in this novel interval, detected a nonsense mutation (p.Q1010*) in the CLIP1 gene. CLIP1 encodes a member of microtubule (MT) plus-end tracking proteins, which specifically associates with the ends of growing MTs. These proteins regulate MT dynamic behavior and are important for MT-mediated transport over the length of axons and dendrites. As such, CLIP1 may have a role in neuronal development. We studied lymphoblastoid and skin fibroblast cell lines established from healthy and affected patients. RT-PCR and western blot analyses showed the absence of CLIP1 transcript and protein in lymphoblastoid cells derived from affected patients. Furthermore, immunofluorescence analyses showed MT plus-end staining only in fibroblasts containing the wild-type (and not the mutant) CLIP1 protein. Collectively, our data suggest that defects in CLIP1 may lead to ARID.
authors.affiliation: Genetics Research Center (GRC), University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Farzaneh
authors.initials: F
authors.lastname: Larti
authors.affiliation: Genetics Research Center (GRC), University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Kimia
authors.initials: K
authors.lastname: Kahrizi
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: 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 (GRC), University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Elahe
authors.initials: E
authors.lastname: Papari
authors.affiliation: Genetics Research Center (GRC), University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Fattahi
authors.affiliation: Genetics Research Center (GRC), University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Niloofar
authors.initials: N
authors.lastname: Bazazzadegan
authors.affiliation: Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Genetics Research Center (GRC), University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Banan
authors.affiliation: Department of Human Molecular Genetics, Max-Planck Institute for Molecular Genetics, Berlin, Germany.
authors.forename: Masoud
authors.initials: M
authors.lastname: Garshasbi
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: H Hilger
authors.initials: HH
authors.lastname: Ropers
authors.affiliation: Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Niels
authors.initials: N
authors.lastname: Galjart
authors.affiliation: Genetics Research Center (GRC), University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Najmabadi
mesh_terms: D000328:Adult; D018389:Codon, Nonsense; D003241:Consanguinity; D005260:Female; D005808:Genes, Recessive; D008040:Genetic Linkage; D056426:Genetic Loci; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D018389:Codon, Nonsense; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; C076744:cytoplasmic linker protein 170