The coding region of TP53INP2, a gene expressed in the developing nervous system, is not altered in a family with autosomal recessive non-progressive infantile ataxia on chromosome 20q11-q13

Authors

  • Jennifer S. Bennetts,

    1. Institute for Molecular Bioscience, The University of Queensland, Australia
    Current affiliation:
    1. GW Hooper Foundation, University of California, San Francisco, 513 Parnassus Ave, San Francisco, CA 94143-0552
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  • Nanna D. Rendtorff,

    1. Wilhelm Johannsen Centre for Functional Genomics, Institute of Medical Biochemistry and Genetics, University of Copenhagen, Copenhagen, Denmark
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  • Fiona Simpson,

    1. Institute for Molecular Bioscience, The University of Queensland, Australia
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  • Lisbeth Tranebjaerg,

    1. Wilhelm Johannsen Centre for Functional Genomics, Institute of Medical Biochemistry and Genetics, University of Copenhagen, Copenhagen, Denmark
    2. Department of Audiology, Bispebjerg Hospital, Copenhagen, Denmark
    3. Department of Medical Genetics, University Hospital, N-Tromsø, Norway
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  • Carol Wicking

    Corresponding author
    1. Institute for Molecular Bioscience, The University of Queensland, Australia
    • Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, Queensland, Australia
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Abstract

The locus for autosomal recessive infantile cerebellar ataxia (CLA3 or SCAR6) has been mapped to chromosome 20q11-q13 in a single Norwegian pedigree. We identified a relatively uncharacterised mouse gene Tp53inp2, and showed that its human orthologue mapped within this candidate interval. Tp53inp2 appears to encode a mammalian-specific protein with homology to the two Tp53inp1 isoforms that respond to cellular stress and interact with p53. We show that Tp53inp2 expression is highly restricted during mouse embryogenesis, with strong expression in the developing brain and spinal cord, as well as in the sensory and motor neuron tracts of the peripheral nervous system. Given this expression pattern, the neurological phenotype of CLA3 and the chromosomal localisation of TP53INP2, we searched the coding region for mutations in samples from individuals from the CLA3 pedigree. Our failure to detect causative mutations suggests that alterations in the coding region of TP53INP2 are not responsible for ataxia in this family, although we cannot rule out changes in non-coding elements of this gene. Developmental Dynamics 236:843–852, 2007. © 2007 Wiley-Liss, Inc.

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