Joubert Syndrome 31

A number sign (#) is used with this entry because of evidence that Joubert syndrome-31 (JBTS31) is caused by homozygous or compound heterozygous mutation in the CEP120 gene (613446) on chromosome 5q23.

Biallelic mutations in the CEP120 gene have also been reported in patients with short-rib thoracic dysplasia-13 (SRTD13; 616300).

For a general phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see JBTS1 (213300).

Clinical Features

Roosing et al. (2016) reported 4 probands diagnosed with Joubert syndrome who had biallelic mutations in the CEP120 gene, including a 4.5-year-old girl from Italy (COR391), an 11-year-old boy from the United States (MTI-143), a 2-year-old boy from Palestine (MTI-991), and a 2-year-old girl from India (MTI-1516). All 4 patients presented with a neurologic phenotype consisting of hypotonia, developmental delay, and cognitive impairment, and all exhibited the molar tooth sign. Ataxia and neonatal breathing abnormalities were reported in 2 patients (MTI-143 and MTI-1516), and patient MTI-143 also had abnormal ocular movements. None of the 4 showed involvement of other organs such as retina, kidneys, liver, or skeleton.

Molecular Genetics

Roosing et al. (2016) performed exome sequencing in a cohort of 145 patients with Joubert syndrome, including 15 children diagnosed with orofaciodigital syndrome type VI (OFD6; 277170), and also screened a panel of 120 known and candidate ciliopathy genes, including CEP120, in a cohort of 346 probands with a phenotype consistent with Joubert syndrome or related ciliopathies. In 4 (0.8%) of the 491 JBTS patients, the authors identified homozygous or compound heterozygous mutations in the CEP120 gene (see, e.g., 613446.0004-613446.0008). Noting that all 4 patients had a relatively mild, purely neurologic phenotype, whereas other patients with mutations in CEP120 exhibit a more complex and severe phenotype (see SRTD13, 616300), Roosing et al. (2016) stated that the mechanism through which mutations in the same gene cause such wide phenotypic variability remained unexplained.