Joubert Syndrome 28

A number sign (#) is used with this entry because of evidence that Joubert syndrome-28 (JBTS28) is caused by homozygous or compound heterozygous mutation in the MKS1 gene (609883) on chromosome 17q22.

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

Clinical Features

Romani et al. (2014) reported 2 unrelated patients, a 44-year-old man (COR340) and a 2-year-old child (COR413), with a relatively mild form of Joubert syndrome. Both had developmental delay, oculomotor abnormalities such as nystagmus or oculomotor apraxia, hypotonia and/or ataxia, and the molar tooth sign on brain imaging. In the text, patient COR413 was reported to have normal intellectual abilities, but in Table 1, patient COR413 was noted to have intellectual disability. The 44-year-old man had retinal dystrophy and intellectual disability, but other organ systems were not involved in either case.

Inheritance

The transmission pattern of JBTS28 in the families reported by Romani et al. (2014) was consistent with autosomal recessive inheritance.

Molecular Genetics

In 2 unrelated individuals with JBTS28, Romani et al. (2014) identified biallelic mutations in the MKS1 gene (609883.0010-609883.0012). The mutations segregated with the disorder in the families and were not found in public databases. Functional studies of the variants and studies of patient cells were not performed. The patients were part of a group of 260 JBTS patients who were screened for mutations in ciliopathy genes.