Joubert syndrome-related disorders (JSRDs) are a group of clinically and genetically heterogeneous conditions that share a midbrain-hindbrain malformation, the molar tooth sign (MPS) visible on brain imaging, with variable neurological, ocular, and renal manifestations. Mutations in the CEP290 gene were recently identified in families with the MTS-related neurological features, many of which showed oculo-renal involvement typical of Senior-Löken syndrome (JSRD-SLS phenotype). Here, we performed comprehensive CEP290-mutation analysis on two nonoverlapping cohorts of JSRD-affected patients with a proven MTS. We identified mutations in 19 of 44 patients with JSRD-SLS. The second cohort consisted of 84 patients representing the spectrum of other JSRD subtypes, with mutations identified in only two patients. The data suggest that CEP290 mutations are frequently encountered and are largely specific to the JSRD-SLS subtype. One patient with mutation displayed complete situs inversus, confirming the clinical and genetic overlap between JSRDs and other ciliopathies.
Bibliographical noteFunding Information:
This work was supported by grants from the U.S. National Institute of Neurological Disease and Stroke, the Italian Ministry of Health (Ricerca Corrente 2007; Ricerca Finalizzata 2005 Progetto Malattie Rare grant number 526/A36), the Fondazione Pierfranco e Luisa Mariani Organizzazione Non Lucrativa di Utilita Sociale, the March of Dimes, the Burroughs Wellcome Fund Award in Translational Research, and the National Institutes of Health.