Correlation of Genetic and Clinical Findings in Spanish Patients with X-linked Juvenile Retinoschisis

Riveiro-Álvarez, Rosa; Trujillo-Tiebas, M J; Giménez-Pardo, A; Garcia‐Hoyos, Maria; López-Martínez, Miguel-Ángel; Aguirre-Lambán, Jana; Garcı́a-Sandoval, Blanca; Pozo, S. Vázquez-Fernández del; Cantalapiedra, Diego; Ávila-Fernández, Almudena; Baiget, Montserrat; Ramos, Carmen; Ayuso, Carmen

doi:10.1167/iovs.09-3418

Cited by 31 publications

(18 citation statements)

References 18 publications

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“…Given the high number of RS1 mutations, several studies investigated a possible correlation between genotype and phenotype. Even though some reports describe a correlation between specific variations and the severity of clinical phenotype (22,23), the majority of published studies found that XLRS patients had relatively uniform clinical manifestations, although with great intra-familial variation in age at onset and progression (1,(24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

Long-term rearrangement of retinal structures in a novel mutation of X-linked retinoschisis

Piermarocchi

Miotto²,

Colavito³

et al. 2017

Biomedical Reports

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The aim of the present study was to report a novel mutation in the retinoschisin 1 (RS1) gene in a Caucasian family affected by X-linked juvenile retinoschisis (XLRS) and to describe the long-term modification of retinal structure. Two brothers with an early onset maculopathy were diagnosed with XLRS. Fundus photography, fluorescein angiography, spectral domain optical coherence tomography and electroretinogram analyses were performed. Their sister was also examined. All subjects were screened for mutations in the RS1 gene. XLRS patients demonstrated a marked reduction of best-corrected visual acuity. SD-OCT scans reported a cystic degeneration primarily involving the inner nuclear layer, though some cysts were detected in the outer plexiform layer and in the ganglion cell layer. During the ten-year follow-up, a progressive retinal thickening and coalescence of the cysts was observed. Genetic testing revealed a novel mutation (p.Ile212Asn) in the RS1 gene in both XLRS patients, whereas their sister was not a genetic carrier. Several mutations of the RS1 gene were recognized to be responsible for XLRS. Although the correspondence between genotype and phenotype is still under debate, is reasonable that siblings affected by XLRS could share other genetic and/or epigenetic factors capable to influence clinical course of the disease.

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Section: Discussionmentioning

confidence: 99%

Long-term rearrangement of retinal structures in a novel mutation of X-linked retinoschisis

Piermarocchi

Miotto²,

Colavito³

et al. 2017

Biomedical Reports

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“…Multiple studies reporting clinical features of XLRS in a series of families have been reported world-wide (Apushkin et al, 2005b; Atchaneeyasakul et al, 2010; Eksandh et al, 2000; Forsius et al, 1963; George et al, 1995, 1996; Hewitt et al, 2005; Kellner et al, 1990; Lesch et al, 2008; Pimenides et al, 2005; Renner et al, 2008; Riveiro-Alvarez et al, 2009; Shinoda et al, 2000; Shukla et al, 2007; Simonelli et al, 2003; Vainio-Mattila et al, 1969; Xu et al, 2011). The penetrance of XLRS is almost complete but clinical expression is highly variable (Sieving, 1998).…”

Section: Clinical Findings Of Congenital Xlrsmentioning

confidence: 99%

X-linked juvenile retinoschisis: Clinical diagnosis, genetic analysis, and molecular mechanisms

Molday

Kellner²,

Weber

2012

Progress in Retinal and Eye Research

266

272

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X-linked juvenile retinoschisis (XLRS, MIM 312700) is a common early onset macular degeneration in males characterized by mild to severe loss in visual acuity, splitting of retinal layers, and a reduction in the b-wave of the electroretinogram (ERG). The RS1 gene (MIM 300839) associated with the disease encodes retinoschisin, a 224 amino acid protein containing a discoidin domain as the major structural unit, an N-terminal cleavable signal sequence, and regions responsible for subunit oligomerization. Retinoschisin is secreted from retinal cells as a disulphide-linked homo-octameric complex which binds to the surface of photoreceptors and bipolar cells to help maintain the integrity of the retina. Over 190 disease-causing mutations in the RS1 gene are known with most mutations occurring as non-synonymous changes in the discoidin domain. Cell expression studies have shown that disease-associated missense mutations in the discoidin domain cause severe protein misfolding and retention in the endoplasmic reticulum, mutations in the signal sequence result in aberrant protein synthesis, and mutations in regions flanking the discoidin domain cause defective disulphide-linked subunit assembly, all of which produce a non-functional protein. Knockout mice deficient in retinoschisin have been generated and shown to display most of the characteristic features found in XLRS patients. Recombinant adeno-associated virus (rAAV) mediated delivery of the normal RS1 gene to the retina of young knockout mice result in long term retinoschisin expression and rescue of retinal structure and function providing a ‘proof of concept’ that gene therapy may be an effective treatment for XLRS.

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“…The RS1 RNA transcript contains 3040 nucleotides [15], and the RS1 protein, expressed in photoreceptor and bipolar cells as a homo‐oligomeric protein complex, is involved in maintaining retinal integrity [16,17]. Although over 190 unique variants in the RS1 gene have been reported and studied in XLRS patients, the severity of visual impairment of XLRS does not correlate strongly with mutation type [18–24].…”

Section: Introductionmentioning

confidence: 99%

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

Huang

Chen

Tsai

2015

The Kaohsiung J of Med Scie

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X-linked retinoschisis (XLRS) is one of the leading causes of macular degeneration in male children. The purpose of this study is to describe the clinical characteristics of a Taiwanese family with X-linked retinoschisis (XLRS) and to investigate the genetic mutation in the retinoschisin 1 (RS1) gene. A total of four participants in this XLRS family were analyzed. Complete ophthalmic examinations were performed, including best corrected visual acuity, optical coherence tomography (OCT), and electroretinogram (ERG). Direct DNA sequence of the RS1 gene identified one affected male and one female carrier. The affected male, had a cartwheel-like macular appearance and abnormal retinal pigment epithelium pigmentation in his bilateral eyes. The mixed scotopic ERG b-wave was more reduced than a-wave. OCT revealed typical macular microcystic schisis cavities. Direct DNA sequence analysis revealed a single base pair substitution in Exon 4, 304C > T, resulting in Arg102Trp. Our results show a RS1 (304C > T) mutation in a Taiwanese family with XLRS. This finding expands the clinical profiles of RS1 mutation and may help to further understand its pathogenesis.

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Correlation of Genetic and Clinical Findings in Spanish Patients with X-linked Juvenile Retinoschisis

Cited by 31 publications

References 18 publications

Long-term rearrangement of retinal structures in a novel mutation of X-linked retinoschisis

Long-term rearrangement of retinal structures in a novel mutation of X-linked retinoschisis

X-linked juvenile retinoschisis: Clinical diagnosis, genetic analysis, and molecular mechanisms

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

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