title: 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.
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.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, Australia.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Bennetts
authors.forename: Nanna D
authors.initials: ND
authors.lastname: Rendtorff
authors.forename: Fiona
authors.initials: F
authors.lastname: Simpson
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Tranebjaerg
authors.forename: Carol
authors.initials: C
authors.lastname: Wicking
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics*; D019295:Computational Biology; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007223:Infant; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009420:Nervous System / Q000196:embryology / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D020754:Spinocerebellar Ataxias / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D020033:Protein Isoforms; C501283:TP53INP2 protein, human