ORPHA: 3156; DO: 0050576;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1q43-q44 | Senior-Loken syndrome 7 | 613615 | Autosomal recessive | 3 | SDCCAG8 | 613524 |
A number sign (#) is used with this entry because of evidence that Senior-Loken syndrome-7 (SLSN7), a ciliopathy, is caused by homozygous or compound heterozygous mutation in the SDCCAG8 gene (613524) on chromosome 1q43.
Mutation in SDCCAG8 can also result in Bardet-Biedl syndrome-16 (BBS16; 615993).
For a phenotypic description and a discussion of genetic heterogeneity of Senior-Loken syndrome, see 266900.
Tay and Vincent (2020) described a 15-year-old girl with SLSN7 and intracranial hypertension. She initially presented at age 10 years with a severe rod-cone retinal dystrophy. Shortly thereafter, she developed renal failure requiring dialysis and subsequent renal transplant and immunosuppression. At age 15, she developed headaches, reduced vision, and clinical findings of papilledema. Lumbar puncture demonstrated an elevated opening pressure of 37 cmH2O (normal, 10-25 cmH2O), and neuroimaging was unremarkable. Tay and Vincent (2020) concluded that the etiology of the patient's intracranial hypertension was likely multifactorial, including the underlying ciliopathy, renal transplantation, immunosuppressant medications, and/or weight gain.
The transmission pattern of SLSN7 in the families reported by Otto et al. (2010) and Tay and Vincent (2020) was consistent with autosomal recessive inheritance.
Otto et al. (2010) used homozygosity mapping followed by exon capture and massively parallel sequencing to identify a homozygous truncating mutation in the SDCCAG8 gene (613524.0001) in 2 sibs with Senior-Loken syndrome-7, who were born of consanguineous parents from Reunion Island. Both patients had biopsy-confirmed nephronophthisis and retinal degeneration, leading to blindness in 1. The authors identified homozygous mutations in SDCCAG8 in 5 other families with a phenotype consistent with Senior-Loken syndrome (see, e.g., 613524.0002-613524.0003). Recessive SDCCAG8 mutations accounted for 3.3% (6 of 182) cases from a worldwide SLSN cohort.
In a 15-year-old girl, born of nonconsanguineous parents, with SLSN7, Tay and Vincent (2020) identified compound heterozygous mutations in the SDCCAG8 gene, a splice site mutation (613524.0004) and a 1-bp duplication (613524.0008). The mutations, which were found by next-generation sequencing, segregated with the disorder in the family. The splice site mutation had previously been identified in a patient with Bardet-Biedl syndrome-16 (BBS16; 615993).
Otto, E. A., Hurd, T. W., Airik, R., Chaki, M., Zhou, W., Stoetzel, C., Patil, S. B., Levy, S., Ghosh, A. K., Murga-Zamalloa, C. A., van Reeuwijk, J., Letteboer, S. J. F., and 43 others. Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy. Nature Genet. 42: 840-850, 2010. [PubMed: 20835237] [Full Text: https://doi.org/10.1038/ng.662]
Tay, S. A., Vincent, A. L. Senior-Loken syndrome and intracranial hypertension. Ophthalmic Genet. 41: 354-357, 2020. [PubMed: 32432520] [Full Text: https://doi.org/10.1080/13816810.2020.1766086]