Cancer Institute A national cancer institute
designated cancer center

Jeffrey Axelrod

Publication Details

  • A Homozygous Mutation in Human PRICKLE1 Causes an Autosomal-Recessive Progressive Myoclonus Epilepsy-Ataxia Syndrome AMERICAN JOURNAL OF HUMAN GENETICS Bassuk, A. G., Wallace, R. H., Buhr, A., Buller, A. R., Afawi, Z., Shimojo, M., Miyata, S., Chen, S., Gonzalez-Alegre, P., Griesbach, H. L., Wu, S., Nashelsky, M., Vladar, E. K., Antic, D., Ferguson, P. J., Cirak, S., Voit, T., Scott, M. P., Axelrod, J. D., Gurnett, C., Daoud, A. S., Kivity, S., Neufeld, M. Y., Mazarib, A., Straussberg, R., Walid, S., Korczyn, A. D., Slusarski, D. C., Berkovic, S. F., El-Shanti, H. I. 2008; 83 (5): 572-581


    Progressive myoclonus epilepsy (PME) is a syndrome characterized by myoclonic seizures (lightning-like jerks), generalized convulsive seizures, and varying degrees of neurological decline, especially ataxia and dementia. Previously, we characterized three pedigrees of individuals with PME and ataxia, where either clinical features or linkage mapping excluded known PME loci. This report identifies a mutation in PRICKLE1 (also known as RILP for REST/NRSF interacting LIM domain protein) in all three of these pedigrees. The identified PRICKLE1 mutation blocks the PRICKLE1 and REST interaction in vitro and disrupts the normal function of PRICKLE1 in an in vivo zebrafish overexpression system. PRICKLE1 is expressed in brain regions implicated in epilepsy and ataxia in mice and humans, and, to our knowledge, is the first molecule in the noncanonical WNT signaling pathway to be directly implicated in human epilepsy.

    View details for DOI 10.1016/j.ajhg.2008.10.003

    View details for Web of Science ID 000261006900003

    View details for PubMedID 18976727

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