#614815
Table of Contents
A number sign (#) is used with this entry because of evidence that Joubert syndrome-18 (JBTS18) is caused by homozygous mutation in the TCTN3 gene (613847) on chromosome 10q24.
Mutation in the TCTN3 gene can also cause a form of orofaciodigital syndrome, OFD4 (258860).
For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.
Thomas et al. (2012) studied 2 sibs, aged 13 and 6 years, from a consanguineous Turkish family with Joubert syndrome. Both sibs had vermis agenesis and the molar tooth sign as well as severe kyphoscoliosis. The older sib also had polydactyly and camptodactyly, abnormal eye movements, breathing anomalies, severe mental retardation, and joint laxity, whereas the younger sib had intrauterine growth retardation, oral anomalies, micrognathia, horseshoe kidney, and ventricular septal defect.
Huppke et al. (2015) reported a boy with JBTS18 who presented at age 12 years with an ataxic gait and severely impaired intellectual development. At birth, he was noted to have postaxial polydactyly of the left foot. At age 5 months, he showed developmental delay and hypotonia. He could sit at age 18 months and could walk unsupported at age 4 years. He had initially been diagnosed with autism because of a lack of social interaction and repetitive behaviors and rituals. Brain MRI showed enlargement of the fourth ventricle and the molar tooth sign with vermis hypoplasia and thickened cerebellar peduncles.
Thomas et al. (2012) analyzed genomewide linkage scans in families with Joubert syndrome that were excluded by linkage to known Joubert syndrome loci and identified a Turkish family with 3 homozygous regions, the largest of which was on chromosome 10 in a region encompassing the TCTN3 gene.
The transmission pattern of Joubert syndrome-18 in the family reported by Thomas et al. (2012) was consistent with autosomal recessive inheritance.
By direct sequencing of the TCTN3 in 2 Turkish sibs with Joubert syndrome, Thomas et al. (2012) identified homozygosity for the same missense mutation in both (G314R; 613847.0006).
In a 12-year-old boy, born of first-cousin Persian parents, with Joubert syndrome, Huppke et al. (2015) identified homozygosity for a splice site mutation in the TCTN3 gene (613847.0007).
Huppke, P., Wegener, E., Bohrer-Rabel, H., Bolz, H. J., Zoll, B., Gartner, J., Bergmann, C. Tectonic gene mutations in patients with Joubert syndrome. Europ. J. Hum. Genet. 23: 616-620, 2015. [PubMed: 25118024, images, related citations] [Full Text]
Thomas, S., Legendre, M., Saunier, S., Bessieres, B., Alby, C., Bonniere, M., Toutain, A., Loeuillet, L., Szymanska, K., Jossic, F., Gaillard, D., Yacoubi, M. T., and 14 others. TCTN3 mutations cause Mohr-Majewski syndrome. Am. J. Hum. Genet. 91: 372-378, 2012. [PubMed: 22883145, images, related citations] [Full Text]
ORPHA: 2754, 475; DO: 0110987;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 10q24.1 | Joubert syndrome 18 | 614815 | Autosomal recessive | 3 | TCTN3 | 613847 |
A number sign (#) is used with this entry because of evidence that Joubert syndrome-18 (JBTS18) is caused by homozygous mutation in the TCTN3 gene (613847) on chromosome 10q24.
Mutation in the TCTN3 gene can also cause a form of orofaciodigital syndrome, OFD4 (258860).
For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.
Thomas et al. (2012) studied 2 sibs, aged 13 and 6 years, from a consanguineous Turkish family with Joubert syndrome. Both sibs had vermis agenesis and the molar tooth sign as well as severe kyphoscoliosis. The older sib also had polydactyly and camptodactyly, abnormal eye movements, breathing anomalies, severe mental retardation, and joint laxity, whereas the younger sib had intrauterine growth retardation, oral anomalies, micrognathia, horseshoe kidney, and ventricular septal defect.
Huppke et al. (2015) reported a boy with JBTS18 who presented at age 12 years with an ataxic gait and severely impaired intellectual development. At birth, he was noted to have postaxial polydactyly of the left foot. At age 5 months, he showed developmental delay and hypotonia. He could sit at age 18 months and could walk unsupported at age 4 years. He had initially been diagnosed with autism because of a lack of social interaction and repetitive behaviors and rituals. Brain MRI showed enlargement of the fourth ventricle and the molar tooth sign with vermis hypoplasia and thickened cerebellar peduncles.
Thomas et al. (2012) analyzed genomewide linkage scans in families with Joubert syndrome that were excluded by linkage to known Joubert syndrome loci and identified a Turkish family with 3 homozygous regions, the largest of which was on chromosome 10 in a region encompassing the TCTN3 gene.
The transmission pattern of Joubert syndrome-18 in the family reported by Thomas et al. (2012) was consistent with autosomal recessive inheritance.
By direct sequencing of the TCTN3 in 2 Turkish sibs with Joubert syndrome, Thomas et al. (2012) identified homozygosity for the same missense mutation in both (G314R; 613847.0006).
In a 12-year-old boy, born of first-cousin Persian parents, with Joubert syndrome, Huppke et al. (2015) identified homozygosity for a splice site mutation in the TCTN3 gene (613847.0007).
Huppke, P., Wegener, E., Bohrer-Rabel, H., Bolz, H. J., Zoll, B., Gartner, J., Bergmann, C. Tectonic gene mutations in patients with Joubert syndrome. Europ. J. Hum. Genet. 23: 616-620, 2015. [PubMed: 25118024] [Full Text: https://doi.org/10.1038/ejhg.2014.160]
Thomas, S., Legendre, M., Saunier, S., Bessieres, B., Alby, C., Bonniere, M., Toutain, A., Loeuillet, L., Szymanska, K., Jossic, F., Gaillard, D., Yacoubi, M. T., and 14 others. TCTN3 mutations cause Mohr-Majewski syndrome. Am. J. Hum. Genet. 91: 372-378, 2012. [PubMed: 22883145] [Full Text: https://doi.org/10.1016/j.ajhg.2012.06.017]
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