Mutations in the AHI1 gene, encoding Jouberin, cause Jeubert syndrome with cortical polymicrogyria

Tracy Dixon-Salazar, Jennifer L. Silhavy, Sarah E. Marsh, Carrie M. Louie, Lesley C. Scott, Aithala Gururaj, Lihadh Al-Gazali, Asma A. Al-Tawari, Hulya Kayserili, László Sztriha, Joseph G. Gleeson

Research output: Contribution to journalArticlepeer-review

255 Citations (Scopus)


Joubert syndrome (JS) is an autosomal recessive disorder marked by agenesis of the cerebellar vermis, ataxia, hypotonia, oculomotor apraxia, neonatal breathing abnormalities, and mental retardation. Despite the fact that this condition was described >30 years ago, the molecular basis has remained poorly understood. Here, we identify two frameshift mutations and one missense mutation in the AHI1 gene in three consanguineous families with JS, some with cortical polymicrogyria. AHI1, encoding the Jouberin protein, is an alternatively spliced signaling molecule that contains seven Trp-Asp (WD) repeats, an SH3 domain, and numerous SH3-binding sites. The gene is expressed strongly in embryonic hindbrain and forebrain, and our data suggest that AHI1 is required for both cerebellar and cortical development in humans. The recently described mutations in NPHP1, encoding a protein containing an SH3 domain, in a subset of patients with JS plus nephronophthisis, suggest a shared pathway.

Original languageEnglish
Pages (from-to)979-987
Number of pages9
JournalAmerican Journal of Human Genetics
Issue number6
Publication statusPublished - Dec 2004

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Mutations in the AHI1 gene, encoding Jouberin, cause Jeubert syndrome with cortical polymicrogyria'. Together they form a unique fingerprint.

Cite this