#614464
Table of Contents
Other entities represented in this entry:
A number sign (#) is used with this entry because Joubert syndrome-15 (JBTS15) is caused by homozygous mutation in the CEP41 gene (610523) on chromosome 7q32. Digenic inheritance has also been reported; see MOLECULAR GENETICS.
Joubert syndrome-15 (JBTS15) is an autosomal recessive developmental disorder characterized by ataxia, hypotonia, delayed psychomotor development, and variable mental retardation. Other features, such as polydactyly, breathing abnormalities, and oculomotor apraxia, are variable (summary by Lee et al., 2012).
For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.
Lee et al. (2012) reported 8 patients from 3 consanguineous families with Joubert syndrome. All patients had hypotonia, ataxia, psychomotor delay with mental retardation, and the molar tooth sign on brain imaging. More variable features included postaxial polydactyly, breathing abnormalities, and oculomotor apraxia. Seven of the patients did not have hepatic or renal involvement; 2 had retinal involvement.
The transmission pattern of Joubert syndrome-15 in the families reported by Lee et al. (2012) was consistent with autosomal recessive inheritance.
By linkage analysis of a consanguineous Egyptian family with Joubert syndrome, Lee et al. (2012) mapped a novel locus, which they termed JBTS15, to a 5-Mb region on chromosome 7q31.33-q32.3 between markers rs766240 and rs4728251 (maximum multipoint lod score of 3.71).
In affected members of 3 consanguineous families with Joubert syndrome-15, 2 of Egyptian origin and 1 Portuguese, Lee et al. (2012) identified 3 different homozygous loss-of-function mutations in the CEP41 gene (610523.0001-610523.0003). The first mutation was found by linkage analysis followed by candidate gene sequencing in 1 of the families. Heterozygous CEP41 mutations (see, e.g., 610523.0004-610523.0007) were found in 5 additional patients with Joubert syndrome, and 3 of them were found to carry heterozygous mutations in other genes associated with ciliopathies (KIF7, 611254.0007 and CC2D2A, 612013.0007 and 612013.0009). These findings indicated digenic inheritance, and suggested that CEP41 may act as a modifier in the broader class of ciliopathies. Extensive studies in zebrafish and patient fibroblasts suggested that CEP41 mutations cause a defect in the posttranslational modification and glutamylation of tubulin by interfering with the proper transport of TTLL6 (610849), an evolutionarily conserved polyglutamylase enzyme, between the basal body and cilium. The findings implicated tubulin posttranslational modification in the pathogenesis of human ciliary dysfunction.
Lee, J. E., Silhavy, J. L., Zaki, M. S., Schroth, J., Bielas, S. L., Marsh, S. E., Olvera, J., Brancati, F., Iannicelli, M., Ikegami, K., Schlossman, A. M., Merriman, B., and 18 others. CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium. Nature Genet. 44: 193-199, 2012. [PubMed: 22246503, images, related citations] [Full Text]
Other entities represented in this entry:
ORPHA: 220493, 475; DO: 0110984;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 7q32.2 | Joubert syndrome 15 | 614464 | Autosomal recessive | 3 | CEP41 | 610523 |
A number sign (#) is used with this entry because Joubert syndrome-15 (JBTS15) is caused by homozygous mutation in the CEP41 gene (610523) on chromosome 7q32. Digenic inheritance has also been reported; see MOLECULAR GENETICS.
Joubert syndrome-15 (JBTS15) is an autosomal recessive developmental disorder characterized by ataxia, hypotonia, delayed psychomotor development, and variable mental retardation. Other features, such as polydactyly, breathing abnormalities, and oculomotor apraxia, are variable (summary by Lee et al., 2012).
For a phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.
Lee et al. (2012) reported 8 patients from 3 consanguineous families with Joubert syndrome. All patients had hypotonia, ataxia, psychomotor delay with mental retardation, and the molar tooth sign on brain imaging. More variable features included postaxial polydactyly, breathing abnormalities, and oculomotor apraxia. Seven of the patients did not have hepatic or renal involvement; 2 had retinal involvement.
The transmission pattern of Joubert syndrome-15 in the families reported by Lee et al. (2012) was consistent with autosomal recessive inheritance.
By linkage analysis of a consanguineous Egyptian family with Joubert syndrome, Lee et al. (2012) mapped a novel locus, which they termed JBTS15, to a 5-Mb region on chromosome 7q31.33-q32.3 between markers rs766240 and rs4728251 (maximum multipoint lod score of 3.71).
In affected members of 3 consanguineous families with Joubert syndrome-15, 2 of Egyptian origin and 1 Portuguese, Lee et al. (2012) identified 3 different homozygous loss-of-function mutations in the CEP41 gene (610523.0001-610523.0003). The first mutation was found by linkage analysis followed by candidate gene sequencing in 1 of the families. Heterozygous CEP41 mutations (see, e.g., 610523.0004-610523.0007) were found in 5 additional patients with Joubert syndrome, and 3 of them were found to carry heterozygous mutations in other genes associated with ciliopathies (KIF7, 611254.0007 and CC2D2A, 612013.0007 and 612013.0009). These findings indicated digenic inheritance, and suggested that CEP41 may act as a modifier in the broader class of ciliopathies. Extensive studies in zebrafish and patient fibroblasts suggested that CEP41 mutations cause a defect in the posttranslational modification and glutamylation of tubulin by interfering with the proper transport of TTLL6 (610849), an evolutionarily conserved polyglutamylase enzyme, between the basal body and cilium. The findings implicated tubulin posttranslational modification in the pathogenesis of human ciliary dysfunction.
Lee, J. E., Silhavy, J. L., Zaki, M. S., Schroth, J., Bielas, S. L., Marsh, S. E., Olvera, J., Brancati, F., Iannicelli, M., Ikegami, K., Schlossman, A. M., Merriman, B., and 18 others. CEP41 is mutated in Joubert syndrome and is required for tubulin glutamylation at the cilium. Nature Genet. 44: 193-199, 2012. [PubMed: 22246503] [Full Text: https://doi.org/10.1038/ng.1078]
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