Joubert Syndrome 16

A number sign (#) is used with this entry because Joubert syndrome-16 (JBTS16) can be caused by homozygous mutation in the TMEM138 gene (614459) on chromosome 11q12.

Description

Joubert syndrome-16 is an autosomal recessive developmental disorder characterized by the molar tooth sign on brain imaging, oculomotor apraxia, variable coloboma, and rare kidney involvement. The phenotype is indistinguishable from that of JBTS2 (608091) (summary by Lee et al., 2012).

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

Clinical Features

Lee et al. (2012) reported 8 consanguineous Arab families with Joubert syndrome. The phenotype included the molar tooth sign on brain imaging, oculomotor apraxia, variable coloboma, and rare kidney involvement. One patient had polydactyly and a fetus had an encephalocele.

Inheritance

The transmission pattern of Joubert syndrome in the families reported by Lee et al. (2012) was consistent with autosomal recessive inheritance.

Molecular Genetics

By repeat sequencing of candidate genes in 6 consanguineous Arab families with Joubert syndrome showing linkage to the JBTS2 locus (608091) on chromosome 11q13, but who were negative for mutations in the TMEM216 gene (613277), Lee et al. (2012) identified homozygous mutations in the TMEM138 gene (614459.0001-614459.0005). None of the mutations was found in 400 controls. Two additional patients from consanguineous Arab families were also found to carry homozygous TMEM138 mutations.