X‐linked retinoschisis in a female with a heterozygous <i>RS1</i> missense mutation

Saldaña, Manuel; Thompson, Jay Daniel; Monk, Emma; Trump, Dorothy; Long, Vernon; Sheridan, Eamonn

doi:10.1002/ajmg.a.31568

Cited by 17 publications

(18 citation statements)

References 10 publications

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“…5 However, females with overt CXLRS manifestations have been described. [26][27][28] X chromosome inactivation 29 and/or homozygosity 27,28 are implicated. Most recently, Gliem et al 30 reported an RS1 homozygous female with macular atrophy and paracentral ring of autofluorescence suggestive of a cone/cone-rod dystrophy.…”

Section: Discussionmentioning

confidence: 98%

Wide-Field Imaging of Nonexudative and Exudative Congenital X-Linked Retinoschisis

Rao

Robinson

Yonekawa

et al. 2016

Retina

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Section: Discussionmentioning

confidence: 98%

Wide-Field Imaging of Nonexudative and Exudative Congenital X-Linked Retinoschisis

Rao

Robinson

Yonekawa

et al. 2016

Retina

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“…Only 2/9 obligate carriers of XLRS had functional abnormalities in the mfERG (Kim et al, 2007). Female carriers have rarely been reported with retinal abnormalities or visual loss (Gieser and Falls, 1961; Mendoza-Londono et al, 1999; Rodriguez et al, 2005; Saldana et al, 2007; Wu et al, 1985). Retinal alterations and ERG abnormalities were variable.…”

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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“…32 In general females who are heterozygous for an RS1 mutation remain asymptomatic and have no clinical features of the condition, 28 33 although we have recently seen a young girl with the clinical features of XLRS1 and a reduced b-wave on electroretinogram (ERG). 34 The patient has an affected father and is heterozygous for his mutation with no other RS1 mutation. It is likely that she has skewed X inactivation accounting for her clinical features.…”

Section: Clinical Featuresmentioning

confidence: 99%