Senior-Loken Syndrome 8

Watchlist

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

IQCB1, NPHP1, CEP290, NPHP4, WDR19, NPHP3, SDCCAG8, CEP164, INVS, SCLT1, TRAF3IP1, POC1B, TMEM218, RPGRIP1L, DNAJC13, INF2, UMOD, HNF1B, RPGR, ALDH3A2

Drugs

Adeno-associated virus serotype 8 containing the human RdCVF sequence and the human RdCVFL sequence, Combination of three adeno-associated viral vectors of serotype 8 containing the 5'-, the body- and the 3'- coding sequences of human CEP290 fused to inteins

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A number sign (#) is used with this entry because of evidence that Senior-Loken syndrome-8 (SLSN8) is caused by homozygous or compound heterozygous mutation in the WDR19 gene (608151) on chromosome 4p14.

For a general phenotypic description and discussion of genetic heterogeneity of Senior-Loken syndrome, see SLSN1 (266900).

Clinical Features

Coussa et al. (2013) studied a consanguineous French Canadian family with an atypical form of retinitis pigmentosa (RP) as well as renal cysts. The 50-year-old male proband had bilateral visual acuities of hand motion only, with severe constriction of visual fields (5 degrees); electroretinographic responses were undetectable. Fundus examination showed fine bone spicules in the periphery and severely attenuated vessels in both eyes, with slight temporal pallor of the optic discs. The patient also exhibited significant macular atrophy that had a 'bear claw' appearance on fundus autofluorescence. Optical coherence tomography (OCT) revealed considerable thinning of the fovea and a poorly delineated photoreceptor layer with extensive loss of the inner/outer segment junctions, as well as foveal debris. Because the patient had a family history of 'kidney problems,' a pelvic ultrasound was performed, which showed bilateral large exophytic renal cysts, although urinalysis and blood biochemistry were within normal ranges. The patient also had mild cognitive impairment. Other family members with RP included the proband's deceased mother, 4 sisters, and a maternal aunt, several of whom also had subclinical renal cysts.

Molecular Genetics

In 3 unrelated patients with nephronophthisis and retinal dystrophy, Halbritter et al. (2013) identified biallelic mutations in the WDR19 gene (608151.0006-608151.0007 and 608151.0010-608151.0011). The patients were ascertained from a larger cohort of 1,056 patients with nephronophthisis-related disorders who underwent genetic analysis; 2 of the 3 Senior-Loken patients exhibited additional features of a ciliopathy, with dilation of the intrahepatic bile ducts in 1 and pancreatic and hepatic cysts in the other.

In affected members of a consanguineous French Canadian family with retinitis pigmentosa and renal cysts, who were negative for mutation in all known autosomal recessive RP-associated genes, Coussa et al. (2013) performed whole-exome capture and next-generation sequencing and identified homozygosity for a missense mutation in the WDR19 gene (L710S; 608151.0001). Screening of 96 patients with a diagnosis of Senior-Loken syndrome revealed WDR19 mutations in 5 probands (see, e.g., 608151.0006-608151.0007 and 608151.0012-608151.0013).