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Eur J Hum Genet. 2015 Mar;23(3):331-6. doi: 10.1038/ejhg.2014.13. Epub 2014 Feb 26.

A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability.

Author information

1
Genetics Research Center (GRC), University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
2
Department of Human Molecular Genetics, Max-Planck Institute for Molecular Genetics, Berlin, Germany.
3
Department of Cell Biology and Genetics, Erasmus MC, Rotterdam, The Netherlands.

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.

PMID:
24569606
PMCID:
PMC4326716
DOI:
10.1038/ejhg.2014.13
[Indexed for MEDLINE]
Free PMC Article

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