Nature Genetics
36, 1008 - 1013 (2004)
Published online: 22 August 2004; | doi:10.1038/ng1419
There is a Corrigendum (October 2004) associated with this Letter.
Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndromeRussell J Ferland1, 10, Wafaa Eyaid2, 10, Randall V Collura3, Laura D Tully1, R Sean Hill1, Doha Al-Nouri2, Ahmed Al-Rumayyan4, Meral Topcu5, Generoso Gascon6, 7, Adria Bodell1, Yin Yao Shugart8, Maryellen Ruvolo3
& Christopher A Walsh1, 91
Division of Neurogenetics and Howard Hughes Medical Institute, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, NRB 266, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. 2
Department of Pediatrics, King Fahad National Guard Hospital, Riyadh 11426, Kingdom of Saudi Arabia. 3
Department of Anthropology, Harvard University, Cambridge, Massachusetts 02138, USA. 4
Department of Neurology, King Fahad National Guard Hospital, Riyadh 11426, Kingdom of Saudi Arabia. 5
Hacettepe University Faculty of Medicine, Department of Pediatrics, Section of Child Neurology, Ankara 06100, Turkey. 6
Department of Neurosciences, King Faisal Specialist Hospital and Research Centre, Jeddah 21499, Kingdom of Saudi Arabia. 7
Clinical Neurosciences & Pediatrics, Brown University School of Medicine, Providence, Rhode Island 02908, USA. 8
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205, USA. 9
Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts 02115, USA. 10
These authors contributed equally to this work.
Correspondence should be addressed to Christopher A Walsh cwalsh@bidmc.harvard.eduJoubert 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 peduncles1,
2,
3,
4,
5,
6,
7,
8,
9. 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 disturbances5,
6,
7,
8,
10,
11,
12. 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.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
