A novel deletion mutation in RS1 gene caused X-linked juvenile retinoschisis in a Chinese family

Abstract

Purpose X-linked juvenile retinoschisis (XLRS), a leading cause of juvenile macular degeneration, is characterized by a spokewheel pattern in the macular region of the retina and splitting of the neurosensory retina. This study aimed to identify the underlying genetic defect in a Chinese family with XLRS. Methods The proband underwent complete ophthalmic examinations, including fundus examination, fundus autofluorescence, and optical coherence tomography. DNA extracted from proband and his younger brother was screened for mutations in RS1 gene. The detected RS1 mutation was tested in all available family members and 200 healthy controls. Results Reduced visual acuity, spoke-wheel pattern at the fovea, and split retina were observed in the proband. A novel frameshift mutation c.206-207delTG in the RS1 gene, leading to a truncated protein (p.L69fs16X), was identified in the proband and his younger brother. This mutation was not found in any unaffected member or in the healthy controls. The mother of the proband was hemizygous for this mutant allele. Conclusions We identified a novel causative mutation of RS1 in a Chinese family with XLRS. This finding expands the mutation spectrum of RS1 and provides evidence for a phenotype-genotype study in XLRS.

Rs1h−/y exon 3-del rat model of X-linked retinoschisis with early onset and rapid phenotype is rescued by RS1 supplementation

“…However, abnormal morphology was not found in heterozygous Rs1h −/+ females, and we conclude that mutant Rs1h mRNA does not itself cause disease in this rat model. This is consistent with the Rs1h −/y mouse created by Liu et al [ 3 ], and it is also constant with lack of clinical findings for human female RS1 −/+ carriers who with rare exception do not show retinal pathology despite carrying an RS1 nonsense mutant allele [ 47 – 49 ]. Additional supporting evidence comes from supplementing the Rs1h −/y retina with a normal RS1 gene via AAV8- RS1 delivery, as this helped preserve retinal laminar structure in the Rs1h −/y male retina and partial preserved reduced the photoreceptor loss.…”

Requirements for Neurogenin2 during mouse postnatal retinal neurogenesis

“…Three other genes, Sag (Palczewski et al, 1989; Palczewski et al, 1992), Gnat1 (Sauer et al, 1997), and Pde6b (Cote, 2004) are components of the photoactivated transduction machinery. Mutations in several of these genes are associated with human and mouse retinal dystrophies, namely CACNA1F (Bech-Hansen et al, 1998; Strom et al, 1998), Gnat1 (Cameron and Lucas, 2009), NR2E3 (Milam et al, 2002), PDE6B (Cheng et al, 2016), RHO (Dryja et al, 1990), ROM1 (Bascom et al, 1992), Sag/Arestin-1 (Song et al, 2013), Rplll (Yamashita et al, 2009), RS1 (Huang et al, 2014; Molday et al, 2001; Molday et al, 2007; Sauer et al, 1997) and PRPH2 (Khan et al, 2016). We also identified two factors, Zic1 and Ptn, that are upregulated in P2 Neurog2 mutant retinas.…”

The gene mutation in a Taiwanese family with X‐linked retinoschisis

“…Furthermore, in vivo high‐resolution imaging modalities have revealed photoreceptor abnormalities and schisis within the various retinal layers of patients with the XLRS1 mutation [37–39]. The macular schisis could be foveal, extrafoveal, or combined.…”