# 606996

SENIOR-LOKEN SYNDROME 4; SLSN4


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
1p36.31 Senior-Loken syndrome 4 606996 AR 3 NPHP4 607215
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal recessive
HEAD & NECK
Eyes
- Retinitis pigmentosa
- Amblyopia
- Rotary nystagmus
- Severe visual impairment
- Diminished amplitude on ERG
GENITOURINARY
Kidneys
- Nephronophthisis
- End stage renal disease
METABOLIC FEATURES
- Polyuria
- Polydipsia
HEMATOLOGY
- Anemia
MISCELLANEOUS
- Genetic heterogeneity (see 266900 for summary)
- Allelic to nephronophthisis 4 (606966)
MOLECULAR BASIS
- Caused by mutation in the nephrocystin 4 gene (NPHP4, 607215.0006)

TEXT

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).


Description

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.


Clinical Features

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.


Mapping

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.


Inheritance

The transmission pattern of SLSN4 in the patients reported by Otto et al. (2002) was consistent with autosomal recessive inheritance.


Molecular Genetics

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.


REFERENCES

  1. 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, images, related citations] [Full Text]

  2. 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, images, related citations] [Full Text]


Contributors:
Victor A. McKusick - updated : 12/23/2002
Creation Date:
Victor A. McKusick : 5/29/2002
carol : 01/25/2024
alopez : 01/24/2024
carol : 01/04/2024
carol : 01/17/2018
carol : 04/24/2012
carol : 4/24/2012
terry : 3/27/2012
alopez : 3/16/2010
carol : 12/26/2002
carol : 12/26/2002
terry : 12/23/2002
alopez : 6/10/2002

# 606996

SENIOR-LOKEN SYNDROME 4; SLSN4


ORPHA: 3156;   DO: 0050576;  


Phenotype-Gene Relationships

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

TEXT

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).


Description

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.


Clinical Features

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.


Mapping

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.


Inheritance

The transmission pattern of SLSN4 in the patients reported by Otto et al. (2002) was consistent with autosomal recessive inheritance.


Molecular Genetics

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.


REFERENCES

  1. 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]

  2. 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]


Contributors:
Victor A. McKusick - updated : 12/23/2002

Creation Date:
Victor A. McKusick : 5/29/2002

Edit History:
carol : 01/25/2024
alopez : 01/24/2024
carol : 01/04/2024
carol : 01/17/2018
carol : 04/24/2012
carol : 4/24/2012
terry : 3/27/2012
alopez : 3/16/2010
carol : 12/26/2002
carol : 12/26/2002
terry : 12/23/2002
alopez : 6/10/2002