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.
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Acknowledgements
We gratefully thank the affected individuals, their mother and their families for participation and well cooperation in this study. This article is a part of Farzaneh Larti’s PhD project. This work was supported by a grant from the University of Social Welfare and Rehabilitation Sciences, the EU FP7 project GENCODYS, grant no. 241995, and the Netherlands Organization for Scientific Research (ZonMw grant no. 91208002).
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Larti, F., Kahrizi, K., Musante, L. et al. A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability. Eur J Hum Genet 23, 331–336 (2015). https://doi.org/10.1038/ejhg.2014.13
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DOI: https://doi.org/10.1038/ejhg.2014.13
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