Joubert Syndrome 13

A number sign (#) is used with this entry because of evidence that Joubert syndrome-13 (JBTS13) is caused by homozygous or compound heterozygous mutation in the TCTN1 gene (609863) on chromosome 12q24.

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

Clinical Features

Garcia-Gonzalo et al. (2011) reported 2 sisters, born of consanguineous Bangladeshi parents, with Joubert syndrome. Brain MRI showed cerebellar vermis hypoplasia and the molar tooth sign, the characteristic radiographic feature of Joubert syndrome. One girl also had bilateral frontotemporal pachygyria. Ophthalmologic assessment and renal ultrasounds were normal at ages 7 years and 4 years, respectively.

Srour et al. (2015) reported a 27-week-old male fetus with JBTS13. Clinical features in the report were sparse, but included the molar tooth sign on brain imaging, abnormal gyration of the frontal lobes, and limb abnormalities.

Inheritance

The transmission pattern of JBTS13 in the family reported by Srour et al. (2015) was consistent with autosomal recessive inheritance.

Molecular Genetics

By homozygosity mapping followed by candidate gene sequencing, Garcia-Gonzalo et al. (2011) identified a homozygous splice site mutation in the TCTN1 gene (609863.0001) in 2 sisters, born of consanguineous Bangladeshi parents, with JBTS13. The TCTN1 gene was found to interact with multiple other proteins in a large complex that localizes to the transition zone between the basal body and axoneme in cilia.

In a 27-week-old male fetus with JBTS13, Srour et al. (2015) identified compound heterozygous mutations in the TCTN1 gene (609863.0001 and 609863.0002). The mutations were found by whole-exome sequencing. Functional studies and studies of patient cells were not performed.