#617761
Table of Contents
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).
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.
The transmission pattern of Joubert syndrome in the families reported by Roosing et al. (2016) was consistent with autosomal recessive inheritance.
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.
Roosing, S., Romani, M., Isrie, M., Rosti, R. O., Micalizzi, A., Musaev, D., Mazza, T., Al-gazali, L., Altunoglu, U., Boltshauser, E., D'Arrigo, S., De Keersmaeker, B., and 12 others. Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes. J. Med. Genet. 53: 608-615, 2016. [PubMed: 27208211, images, related citations] [Full Text]
ORPHA: 475; DO: 0080277;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 5q23.2 | Joubert syndrome 31 | 617761 | Autosomal recessive | 3 | CEP120 | 613446 |
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).
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.
The transmission pattern of Joubert syndrome in the families reported by Roosing et al. (2016) was consistent with autosomal recessive inheritance.
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.
Roosing, S., Romani, M., Isrie, M., Rosti, R. O., Micalizzi, A., Musaev, D., Mazza, T., Al-gazali, L., Altunoglu, U., Boltshauser, E., D'Arrigo, S., De Keersmaeker, B., and 12 others. Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes. J. Med. Genet. 53: 608-615, 2016. [PubMed: 27208211] [Full Text: https://doi.org/10.1136/jmedgenet-2016-103832]
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