ORPHA: 3156; DO: 0050576;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 12q21.32 | Senior-Loken syndrome 6 | 610189 | Autosomal recessive | 3 | CEP290 | 610142 |
A number sign (#) is used with this entry because of evidence that Senior-Loken syndrome-6 (SLSN6) is caused by homozygous mutation in the NPHP6 gene (CEP290; 610142) on chromosome 12q21.
Mutations in the CEP290 gene can also cause Joubert syndrome-5 (610188).
Senior-Loken syndrome-6 (SLSN6) is an autosomal recessive disorder characterized by the association of nephronophthisis resulting in end-stage renal disease in the second decade of life with retinal degeneration (Sayer et al., 2006).
For a phenotypic description and a discussion of genetic heterogeneity of Senior-Loken syndrome, see 266900.
Sayer et al. (2006) described a Turkish family in which 2 sibs with Senior-Loken syndrome reached end-stage renal disease at 11 and 13 years of age, respectively. Both had tapetoretinal degeneration resulting in reduced vision before 3 years of age.
The transmission pattern of SLSN6 in the family reported by Sayer et al. (2006) was consistent with autosomal recessive inheritance.
Identification of causative mutations in the CEP290 gene in the Turkish family with Senior-Loken syndrome described by Sayer et al. (2006) localized the SLSN6 phenotype to chromosome 12q21.32.
In 2 affected sibs in a Turkish family segregating Senior-Loken syndrome, Sayer et al. (2006) detected a homozygous 5-bp deletion in the CEP290 gene (610142.0004). The mutation altered an obligatory splice site.
Sayer, J. A., Otto, E. A., O'Toole, J. F., Nurnberg, G., Kennedy, M. A., Becker, C., Hennies, H. C., Helou, J., Attanasio, M., Fausett, B. V., Utsch, B., Khanna, H., and 30 others. The centrosomal protein nephrocystin-6 is mutated in Joubert syndrome and activates transcription factor ATF4. Nature Genet. 38: 674-681, 2006. [PubMed: 16682973] [Full Text: https://doi.org/10.1038/ng1786]