Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Ferland, Russell J; Eyaid, Wafaa; Collura, Randall V; Tully, Laura D; Hill, R Sean; Al-Nouri, Doha; Al-Rumayyan, Ahmed; Topcu, Meral; Gascon, Generoso; Bodell, Adria; Shugart, Yin Yao; Ruvolo, Maryellen; Walsh, Christopher A
Year of Publication: 2004
Journal: Nat Genet
Volume: 36
Issue: 9
Pagination: 1008-13
Date Published: 2004 Sep
Publication Language: eng
ISSN: 1061-4036
Keywords: Abnormalities, Multiple, Adaptor Proteins, Signal Transducing, Animals, Brain, Brain Stem, Cerebellum, Developmental Disabilities, Female, Humans, Infant, Magnetic Resonance Imaging, Male, Mice, Molecular Sequence Data, Mutation, Nerve Tissue Proteins, Pedigree, Phylogeny, Syndrome

Joubert syndrome is a congenital brain malformation of the cerebellar vermis and brainstem with abnormalities of axonal decussation (crossing in the brain) affecting the corticospinal tract and superior cerebellar peduncles. Individuals with Joubert syndrome have motor and behavioral abnormalities, including an inability to walk due to severe clumsiness and 'mirror' movements, and cognitive and behavioral disturbances. Here we identified a locus associated with Joubert syndrome, JBTS3, on chromosome 6q23.2-q23.3 and found three deleterious mutations in AHI1, the first gene to be associated with Joubert syndrome. AHI1 is most highly expressed in brain, particularly in neurons that give rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles. Comparative genetic analysis of AHI1 indicates that it has undergone positive evolutionary selection along the human lineage. Therefore, changes in AHI1 may have been important in the evolution of human-specific motor behaviors.

DOI: 10.1038/ng1419
Alternate Journal: Nat. Genet.