ORPHA: 3156; DO: 0050576;
Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
---|---|---|---|---|---|---|
1p36.31 | Senior-Loken syndrome 4 | 606996 | Autosomal recessive | 3 | NPHP4 | 607215 |
A number sign (#) is used with this entry because of evidence that Senior-Loken syndrome-4 (SLSN4) is caused by homozygous mutation in the NPHP4 gene (607215) on chromosome 1p36.
Mutations in the NPHP4 gene can also cause nephronophthisis-4 (606966).
Senior-Loken syndrome-4 (SLSN4) is an autosomal recessive disorder characterized by the association of the cystic renal disorder nephronophthisis with late-onset retinitis pigmentosa (Schuermann et al., 2002).
For a general phenotypic description and a discussion of genetic heterogeneity of Senior-Loken syndrome, see 266900.
Schuermann et al. (2002) reported a family (F3) in which 3 individuals were affected with late-onset retinitis pigmentosa in addition to nephronophthisis, an association described as Senior-Loken syndrome.
In family F3 reported by Schuermann et al. (2002), haplotype analysis of 8 markers at the nephronophthisis-4 locus was compatible with homozygosity by descent in all 3 affected children. Multipoint linkage analysis for these markers yielded a maximum lod score of 2.7, for marker D1S214. This marker is positioned on a physical map, only 0.3 Mb from marker D1S2642, which flanks the NPHP4 region on the centromeric side. The authors referred to the locus on 1p as SLSN4.
The transmission pattern of SLSN4 in the patients reported by Otto et al. (2002) was consistent with autosomal recessive inheritance.
Otto et al. (2002) demonstrated 2 loss-of-function mutations of the NPHP4 gene (607215.0006-607215.0007) in patients with Senior-Loken syndrome from 2 unrelated families.
Otto, E., Hoefele, J., Ruf, R., Mueller, A. M., Hiller, K. S., Wolf, M. T. F., Schuermann, M. J., Becker, A., Birkenhager, R., Sudbrak, R., Hennies, H. C., Nurnberg, P., Hildebrandt, F. A gene mutated in nephronophthisis and retinitis pigmentosa encodes a novel protein, nephroretinin, conserved in evolution. Am. J. Hum. Genet. 71: 1161-1167, 2002. Note: Erratum: Am. J. Hum. Genet.: 71: 1489 only, 2002. [PubMed: 12205563] [Full Text: https://doi.org/10.1086/344395]
Schuermann, M. J., Otto, E., Becker, A., Saar, K., Ruschendorf, F., Polak, B. C., Ala-Mello, S., Hoefele, J., Wiedensohler, A., Haller, M., Omran, H., Nurnberg, P., Hildebrandt, F. Mapping of gene loci for nephronophthisis type 4 and Senior-Loken syndrome, to chromosome 1p36. Am. J. Hum. Genet. 70: 1240-1246, 2002. [PubMed: 11920287] [Full Text: https://doi.org/10.1086/340317]