Joubert syndrome (JBTS) is an autosomal recessive disorder presenting with psychomotor delay, hypotonia, ataxia, oculomotor apraxia, and neonatal breathing abnormalities (Valente et al., 2006). Neuroradiologically, Joubert syndrome is characterized by a peculiar malformation of the midbrain-hindbrain junction known ... Joubert syndrome (JBTS) is an autosomal recessive disorder presenting with psychomotor delay, hypotonia, ataxia, oculomotor apraxia, and neonatal breathing abnormalities (Valente et al., 2006). Neuroradiologically, Joubert syndrome is characterized by a peculiar malformation of the midbrain-hindbrain junction known as the 'molar tooth sign' (MTS) consisting of cerebellar vermis hypoplasia or aplasia, thick and maloriented superior cerebellar peduncles, and abnormally deep interpeduncular fossa. A number of distinct syndromes sharing the MTS have been described, presenting wide phenotypic variability both within and among families (Gleeson et al., 2004). Valente et al. (2006) described the JBTS5 phenotype as characterized mainly by the neurologic and neuroradiologic features of Joubert syndrome associated with severe retinal and renal involvement, but noted that the clinical spectrum was broad, including incomplete phenotypes such as cerebelloretinal and cerebellorenal syndromes. The full-blown JBTS5 phenotype largely overlaps that of Senior-Loken syndrome (SLSN; see 266900), which is characterized by retinitis pigmentosa plus juvenile nephronophthisis and is attributable to mutations in genes associated with nephronophthisis and encoding ciliary proteins.
Upon mutation analysis within the NPHP6 genetic interval, Sayer et al. (2006) identified an identical homozygous nonsense mutation, 5668G-T (G1890X), located in the CEP290 gene (610142.0001), which had been described as a component of the centrosomal proteome (Anderson ... Upon mutation analysis within the NPHP6 genetic interval, Sayer et al. (2006) identified an identical homozygous nonsense mutation, 5668G-T (G1890X), located in the CEP290 gene (610142.0001), which had been described as a component of the centrosomal proteome (Anderson et al., 2003), in 2 kindreds. Further mutation screening in 96 unrelated individuals with JBTS by direct sequencing identified this mutation in a third family. Altogether Sayer et al. (2006) identified 8 distinct mutations in CEP290 in 7 JBTS families. In 5 families with JBTS, Valente et al. (2006) found 5 mutations in the CEP290 gene, including 3 nonsense mutations resulting in premature protein truncation, one 1-bp deletion generating a frameshift and a premature stop codon, and 1 missense mutation (W7C; 610142.0003).