Joubert Syndrome 18

A number sign (#) is used with this entry because of evidence that Joubert syndrome-18 (JBTS18) can be caused by homozygous mutation in the TCTN3 gene (613847) on chromosome 10q24.

Mutation in the TCTN3 gene can also cause a form of orofaciodigital syndrome, OFD4 (258860).

For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.

Clinical Features

Thomas et al. (2012) studied 2 sibs, aged 13 and 6 years, from a consanguineous Turkish family with Joubert syndrome. Both sibs had vermis agenesis and the molar tooth sign as well as severe kyphoscoliosis. The older sib also had polydactyly and camptodactyly, abnormal eye movements, breathing anomalies, severe mental retardation, and joint laxity, whereas the younger sib had intrauterine growth retardation, oral anomalies, micrognathia, horseshoe kidney, and ventricular septal defect.

Mapping

Thomas et al. (2012) analyzed genomewide linkage scans in families with Joubert syndrome that were excluded by linkage to known Joubert syndrome loci and identified a Turkish family with 3 homozygous regions, the largest of which was on chromosome 10 in a region encompassing the TCTN3 gene.

Molecular Genetics

By direct sequencing of the TCTN3 in 2 Turkish sibs with Joubert syndrome, Thomas et al. (2012) identified homozygosity for the same missense mutation in both (G314R; 613847.0006).