Distinguishing the four genetic causes of Jouberts syndrome-related disorders

Enza Maria Valente, Sarah E. Marsh, Marco Castori, Tracy Dixon-Salazar, Enrico Bertini, Lihadh Al-Gazali, Jean Messer, Clara Barbot, C. Geoffrey Woods, Eugen Boltshauser, Asma A. Al-Tawari, Carmelo D. Salpietro, Hulya Kayserili, László Sztriha, Moez Gribaa, Michel Koenig, Bruno Dallapiccola, Joseph G. Gleeson

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)


Jouberts syndrome-related disorders are a group of recessively inherited conditions showing cerebellar vermis hypoplasia and the molar tooth sign of the midbrain-hindbrain junction. Recent analyses have suggested at least three loci, JBTS1 (9q34.3), -2 (11p11.2-q12.3), and -3 (6q23), but the phenotypic spectrum associated with each locus has not been delineated. In addition, deletions of the NPHP1 gene, usually responsible for isolated juvenile nephronophthisis, are occasionally encountered among Jouberts syndrome-related disorder patients. Here, we describe four novel families showing evidence of linkage to two of these loci, provide a 3.6Mb refinement of the JBTS2 locus, and perform a detailed comparison of all linked families identified so far, to define the clinical and radiographical hallmarks for each genetic condition. We find that JBTS1 and -3 primarily show features restricted to the central nervous system, with JBTS1 showing largely pure cerebellar and midbrain-hindbrain junction involvement, and JBTS3 displaying cerebellar, midbrain-hindbrain junction, and cerebral cortical features, most notably polymicrogyria. Conversely, JBTS2 is associated with multiorgan involvement of kidney, retina, and liver, in addition to the central nervous system features, and results in extreme phenotypic variability. This provides a useful framework for genetic testing strategies and prediction of which patients are most likely to experience development of systemic complications.

Original languageEnglish
Pages (from-to)513-519
Number of pages7
JournalAnnals of Neurology
Issue number4
Publication statusPublished - Apr 2005

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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