Mutations in a novel gene encoding a CRAL-TRIO domain cause human Cayman ataxia and ataxia/dystonia in the jittery mouse

Jamee M. Bomar, Paul J. Benke, Eric L. Slattery, Radhika Puttagunta, Larry P. Taylor, Eunju Seong, Arne Nystuen, Weidong Chen, Roger L. Albin, Paresh D. Patel, Rick A. Kittles, Val C. Sheffield, Margit Burmeister

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

Cayman ataxia is a recessive congenital ataxia restricted to one area of Grand Cayman Island. Comparative mapping suggested that the locus on 19p13.3 associated with Cayman ataxia might be homologous to the locus on mouse chromosome 10 associated with the recessive ataxic mouse mutant jittery. Screening genes in the region of overlap identified mutations in a novel predicted gene in three mouse jittery alleles, including the first mouse mutation caused by an Alu-related (B1 element) insertion. We found two mutations exclusively in all individuals with Cayman ataxia. The gene ATCAY or Atcay encodes a neuron-restricted protein called caytaxin. Caytaxin contains a CRAL-TRIO motif common to proteins that bind small lipophilic molecules. Mutations in another protein containing a CRAL-TRIO domain, alpha-tocopherol transfer protein (TTPA), cause a vitamin E-responsive ataxia. Three-dimensional protein structural modeling predicts that the caytaxin ligand is more polar than vitamin E. Identification of the caytaxin ligand may help develop a therapy for Cayman ataxia.

Original languageEnglish (US)
Pages (from-to)264-269
Number of pages6
JournalNature Genetics
Volume35
Issue number3
DOIs
StatePublished - Nov 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

Fingerprint Dive into the research topics of 'Mutations in a novel gene encoding a CRAL-TRIO domain cause human Cayman ataxia and ataxia/dystonia in the jittery mouse'. Together they form a unique fingerprint.

  • Cite this

    Bomar, J. M., Benke, P. J., Slattery, E. L., Puttagunta, R., Taylor, L. P., Seong, E., Nystuen, A., Chen, W., Albin, R. L., Patel, P. D., Kittles, R. A., Sheffield, V. C., & Burmeister, M. (2003). Mutations in a novel gene encoding a CRAL-TRIO domain cause human Cayman ataxia and ataxia/dystonia in the jittery mouse. Nature Genetics, 35(3), 264-269. https://doi.org/10.1038/ng1255