Other entities represented in this entry:
ORPHA: 655; DO: 0111119;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 2q24.3 | Nephronophthisis 12 | 613820 | Autosomal dominant; Autosomal recessive | 3 | TTC21B | 612014 |
A number sign (#) is used with this entry because nephronophthisis-12 (NPHP12) is caused by homozygous or compound heterozygous mutation in the TTC21B gene (612014) on chromosome 2q24. Heterozygous mutation in the TTC21B gene has been found in patients with Joubert syndrome-11 (JBTS11), a related cilopathy.
For a general phenotypic description and a discussion of genetic heterogeneity of NPHP, see 256100.
For a general phenotypic description and a discussion of genetic heterogeneity of Joubert syndrome, see 213300.
In affected members of 2 unrelated consanguineous families with nephronophthisis-12, Davis et al. (2011) identified a homozygous mutation in the TTC21B gene (P209L; 612014.0001). One family was of Portuguese and the other of Egyptian descent. In vitro and in vivo functional expression studies in mammalian cells and zebrafish indicated that the mutant protein was a hypomorphic allele. In 2 additional families with early-onset NPHP with extrarenal manifestations, the P209L allele was found in compound heterozygosity with another pathogenic TTC21B allele: C552X (612014.0002) and a splice site mutation (612014.0003), respectively. Both of the latter mutations were shown by expression studies to be functionally null alleles. Haplotype analysis indicated a founder effect for the P209L allele. In addition, heterozygous functionally pathogenic alleles were found in about 5% of the total cohort, including 3 unrelated patients with Joubert syndrome-11 (JBTS11) suggesting that TTC21B might be a common contributor to the total mutational load in ciliopathies. No clinical details on the patients were provided.
Davis, E. E., Zhang, Q., Liu, Q., Diplas, B. H., Davey, L. M., Hartley, J., Stoetzel, C., Szymanska, K., Ramaswami, G., Logan, C. V., Muzny, D. M., Young, A. C., and 36 others. TTC21B contributes both causal and modifying alleles across the ciliopathy spectrum. Nature Genet. 43: 189-196, 2011. Note: Erratum: Nature Genet. 43: 499 only, 2011. [PubMed: 21258341] [Full Text: https://doi.org/10.1038/ng.756]