Members of the International JSRD Study Group are listed in the Appendix on page xx.
AHI1 gene mutations cause specific forms of Joubert syndrome–related disorders
Article first published online: 1 FEB 2006
Copyright © 2006 American Neurological Association
Annals of Neurology
Volume 59, Issue 3, pages 527–534, March 2006
How to Cite
Valente, E. M., Brancati, F., Silhavy, J. L., Castori, M., Marsh, S. E., Barrano, G., Bertini, E., Boltshauser, E., Zaki, M. S., Abdel-Aleem, A., Abdel-Salam, G. M. H., Bellacchio, E., Battini, R., Cruse, R. P., Dobyns, W. B., Krishnamoorthy, K. S., Lagier-Tourenne, C., Magee, A., Pascual-Castroviejo, I., Salpietro, C. D., Sarco, D., Dallapiccola, B. and Gleeson, J. G. (2006), AHI1 gene mutations cause specific forms of Joubert syndrome–related disorders. Ann Neurol., 59: 527–534. doi: 10.1002/ana.20749
- Issue published online: 17 FEB 2006
- Article first published online: 1 FEB 2006
- Manuscript Revised: 17 OCT 2005
- Manuscript Accepted: 17 OCT 2005
- Manuscript Received: 20 JUL 2005
- NIH (National Institute of Neurological Disease and Stroke. Grant Number: NS4853
- Italian Ministry of Health
- Fondazione Pierfranco e Luisa Mariani ONLUS
- March of Dimes. Grant Number: FY02-148
- Burroughs Wellcome Fund Award in Translational Research
Joubert syndrome (JS) is a recessively inherited developmental brain disorder with several identified causative chromosomal loci. It is characterized by hypoplasia of the cerebellar vermis and a particular midbrain-hindbrain “molar tooth” sign, a finding shared by a group of Joubert syndrome–related disorders (JSRDs), with wide phenotypic variability. The frequency of mutations in the first positionally cloned gene, AHI1, is unknown.
We searched for mutations in the AHI1 gene among a cohort of 137 families with JSRD and radiographically proven molar tooth sign.
We identified 15 deleterious mutations in 10 families with pure JS or JS plus retinal and/or additional central nervous system abnormalities. Mutations among families with JSRD including kidney or liver involvement were not detected. Transheterozygous mutations were identified in the majority of those without history of consanguinity. Most mutations were truncating or splicing errors, with only one missense mutation in the highly conserved WD40 repeat domain that led to disease of similar severity.
AHI1 mutations are a frequent cause of disease in patients with specific forms of JSRD. Ann Neurol 2006