#614970
Table of Contents
A number sign (#) is used with this entry because of evidence that Joubert syndrome-20 (JBTS20) is caused by compound heterozygous mutation in the TMEM231 gene (614949) on chromosome 16q23.
For a general phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.
Srour et al. (2012) reported 3 patients from 2 unrelated French Canadian families with Joubert syndrome. The patients were 14, 9, and 4 years old, respectively. All had developmental delay and were nonverbal and nonambulatory. Other features included oculomotor apraxia, breathing abnormalities, and the molar tooth sign on brain MRI. Two had postaxial polydactyly, 2 had retinal involvement, and 2 had renal cysts with normal renal function. Two sibs in 1 family showed significant aggressive behavior and self-mutilation.
The transmission pattern of JBTS20 in the families reported by Srour et al. (2012) was consistent with autosomal recessive inheritance.
In 3 patients from 2 French Canadian families with Joubert syndrome-20, Srour et al. (2012) identified compound heterozygosity for 2 mutations in the TMEM231 gene (614949.0001 and 614949.0002). The mutations were identified by exome sequencing and confirmed by Sanger sequencing. The TMEM231 gene is a component of a protein complex in the basal body, a ring-like structure that functions in the transition zone at the base of cilia (Chih et al., 2012).
Chih et al. (2012) found that knockout of Tmem231 in mice led to lethality around embryonic day 15.5 with severe vascular defects. The phenotype included microphthalmia and polydactyly, and defects in patterning of the ventral spinal cord, consistent with a ciliopathy. Tmem231 -/- embryos showed loss of cilia and altered Shh (600725) gene expression, including absence of Shh-positive floorplate cells.
Chih, B., Liu, P., Chinn, Y., Chalouni, C., Komuves, L. G., Hass, P. E., Sandoval, W., Peterson, A. S. A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain. Nature Cell Biol. 14: 61-72, 2012. [PubMed: 22179047, related citations] [Full Text]
Srour, M., Hamdan, F. F., Schwartzentruber, J. A., Patry, L., Ospina, L. H., Shevell, M. I., Desilets, V., Dobrzeniecka, S., Mathonnet, G., Lemyre, E., Massicotte, C., Labuda, D., Amrom, D., Andermann, E., Sebire, G., Maranda, B., FORGE Canada Consortium, Rouleau, G. A., Majewski, J., Michaud, J. L. Mutations in TMEM231 cause Joubert syndrome in French Canadians. J. Med. Genet. 49: 636-641, 2012. [PubMed: 23012439, related citations] [Full Text]
ORPHA: 220493, 475; DO: 0110989;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 16q23.1 | Joubert syndrome 20 | 614970 | Autosomal recessive | 3 | TMEM231 | 614949 |
A number sign (#) is used with this entry because of evidence that Joubert syndrome-20 (JBTS20) is caused by compound heterozygous mutation in the TMEM231 gene (614949) on chromosome 16q23.
For a general phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.
Srour et al. (2012) reported 3 patients from 2 unrelated French Canadian families with Joubert syndrome. The patients were 14, 9, and 4 years old, respectively. All had developmental delay and were nonverbal and nonambulatory. Other features included oculomotor apraxia, breathing abnormalities, and the molar tooth sign on brain MRI. Two had postaxial polydactyly, 2 had retinal involvement, and 2 had renal cysts with normal renal function. Two sibs in 1 family showed significant aggressive behavior and self-mutilation.
The transmission pattern of JBTS20 in the families reported by Srour et al. (2012) was consistent with autosomal recessive inheritance.
In 3 patients from 2 French Canadian families with Joubert syndrome-20, Srour et al. (2012) identified compound heterozygosity for 2 mutations in the TMEM231 gene (614949.0001 and 614949.0002). The mutations were identified by exome sequencing and confirmed by Sanger sequencing. The TMEM231 gene is a component of a protein complex in the basal body, a ring-like structure that functions in the transition zone at the base of cilia (Chih et al., 2012).
Chih et al. (2012) found that knockout of Tmem231 in mice led to lethality around embryonic day 15.5 with severe vascular defects. The phenotype included microphthalmia and polydactyly, and defects in patterning of the ventral spinal cord, consistent with a ciliopathy. Tmem231 -/- embryos showed loss of cilia and altered Shh (600725) gene expression, including absence of Shh-positive floorplate cells.
Chih, B., Liu, P., Chinn, Y., Chalouni, C., Komuves, L. G., Hass, P. E., Sandoval, W., Peterson, A. S. A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain. Nature Cell Biol. 14: 61-72, 2012. [PubMed: 22179047] [Full Text: https://doi.org/10.1038/ncb2410]
Srour, M., Hamdan, F. F., Schwartzentruber, J. A., Patry, L., Ospina, L. H., Shevell, M. I., Desilets, V., Dobrzeniecka, S., Mathonnet, G., Lemyre, E., Massicotte, C., Labuda, D., Amrom, D., Andermann, E., Sebire, G., Maranda, B., FORGE Canada Consortium, Rouleau, G. A., Majewski, J., Michaud, J. L. Mutations in TMEM231 cause Joubert syndrome in French Canadians. J. Med. Genet. 49: 636-641, 2012. [PubMed: 23012439] [Full Text: https://doi.org/10.1136/jmedgenet-2012-101132]
Dear OMIM User,
To ensure long-term funding for the OMIM project, we have diversified our revenue stream. We are determined to keep this website freely accessible. Unfortunately, it is not free to produce. Expert curators review the literature and organize it to facilitate your work. Over 90% of the OMIM's operating expenses go to salary support for MD and PhD science writers and biocurators. Please join your colleagues by making a donation now and again in the future. Donations are an important component of our efforts to ensure long-term funding to provide you the information that you need at your fingertips.
Thank you in advance for your generous support,
Ada Hamosh, MD, MPH
Scientific Director, OMIM