Retinal Dystrophy with Intraretinal Cystoid Spaces Associated with Mutations in the Crumbs Homologue (<i>CRB1</i>) Gene

Cordovez, Jose A.; Traboulsi, Elias I.; Capasso, Jenina E.; Sadagopan, Karthikeyan Arcot; Ganesh, Anuradha; Rychwalski, Paul J.; Neely, Kimberly A.; Levin, Alex V.

doi:10.3109/13816810.2014.881505

Cited by 19 publications

(12 citation statements)

References 48 publications

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“…Further studies on CAI treatment showed a rebound effect in RS1 in a small subset of patients only 14. A different response to treatment with oral CAI might be possible for various genotypes in RS1 (including the side effects), as previously reported 15–18…”

Section: Introductionsupporting

confidence: 51%

Rebound macular edema following oral acetazolamide therapy for juvenile X-linked retinoschisis in an Italian family

Galantuomo¹,

Fossarello²,

Cuccu³

et al. 2016

OPTH

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BackgroundJuvenile X-linked retinoschisis (RS1, OMIM: 312700) is a hereditary vitreoretinal dystrophy characterized by bilateral foveal schisis and, in half of the patients, splitting through the nerve fiber layer in the peripheral retina. In the first decade of life, patients usually develop a decrease in visual acuity. Long-term visual outcomes can be poor due to the limited number of known successful treatments.PurposeThe purposes of this study were to present, for the first time, a p.Arg197Cys missense mutation in the RS1 gene (OMIM: 300839) in a four-generation Italian family with RS1 and to examine the clinical response to the treatment with acetazolamide tablets alone or in combination with dorzolamide eye drops as assessed by spectral-domain optical coherence tomography (SD-OCT).MethodsEleven individuals, including two brothers with RS1 (patients 1 and 2), underwent a full medical history examination and a comprehensive ocular assessment that involved SD-OCT, fluorescein angiography, electroretinography and DNA analysis. Each RS1 patient received oral acetazolamide (375 mg daily) during the first three months. Thereafter, patient 1 continued only with dorzolamide eyedrops three times a day for a period of three months, while patient 2 spontaneously stopped both medications.ResultsSequence analysis of the RS1 gene identified a hemizygous c.589C>T (p.Arg197Cys) missense mutation in exon 6, which has not been previously reported in an Italian family. A different response to the medical therapy was observed in the four eyes of the two affected brothers hemizygous for this abnormality. Of note, after acetazolamide interruption, a rebound effect on cystoid macular edema reduced the beneficial effects of the initial therapy for RS1 from p.Arg197Cys mutation. Indeed, a minimal rebound effect on cystoid macular edema, and an improvement in visual acuity, was observed in patient 1 during the six months of treatment. Conversely, in patient 2, an initial improvement in cystoid macular edema was not associated with visual acuity changes, followed by a marked rebound effect.ConclusionThis study showed that the sequential use of acetazolamide tablets and dorzolamide eye drops should be considered and studied further as a possible treatment for macular edema and visual impairment in patients with RS1 from a hemizygous p.Arg197Cys mutation.

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Section: Introductionsupporting

confidence: 51%

Rebound macular edema following oral acetazolamide therapy for juvenile X-linked retinoschisis in an Italian family

Galantuomo¹,

Fossarello²,

Cuccu³

et al. 2016

OPTH

View full text Add to dashboard Cite

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“…The most prominent are hypermetropic refractive error, nummular pigmentation, intraretinal cystoid spaces, retinal thickening with loss/reduced retinal lamination, and occasionally there may also be sparing of para-arteriolar RPE [22,23]; all of these features were observed in proband 3, and lead us to screen CRB1 by Sanger sequencing as an initial approach. In proband 2, with advanced disease, the aforementioned clinical examination features were not readily recognizable and she was initially referred to a geneticist with a diagnosis of autosomal recessive RP, which resulted in genetic screening using an AR RP microarray.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic features of CRB1-associated early-onset severe retinal dystrophy and the different molecular approaches to identifying the disease-causing variants

Kousal

Ďuďáková

Gaillyová

et al. 2016

Graefes Arch Clin Exp Ophthalmol

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The first study reporting on the molecular genetic cause of non-syndromic early-onset severe retinal dystrophy in Czech patients identified one homozygous and two compound heterozygote probands with CRB1 mutations. Retina nerve fibre layer measurements should be considered an integral part of the clinical evaluation of retinal dystrophies. Detailed clinical examination and imaging can both direct molecular screening and help to confirm or refute disease causation of identified variants.

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“…The genes most frequently linked with RP include RHO , USH2A , RPGR , CRB1 , GUCY2D , and RPGPIP1 [11]. Previous studies reported CRB1 mutations in ARRP in diverse populations [2, 11, 12, 14]. This study identified a pair of novel compound mutations in CRB1 in a Chinese pedigree with ARRP.…”

Section: Discussionmentioning

confidence: 80%

Novel mutations in CRB1 gene identified in a chinese pedigree with retinitis pigmentosa by targeted capture and next generation sequencing

Wang

et al. 2016

Oncotarget

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PURPOSETo detect the disease-causing gene in a Chinese pedigree with autosomal-recessive retinitis pigmentosa (ARRP).METHODSAll subjects in this family underwent a complete ophthalmic examination. Targeted-capture next generation sequencing (NGS) was performed on the proband to detect variants. All variants were verified in the remaining family members by PCR amplification and Sanger sequencing.RESULTSAll the affected subjects in this pedigree were diagnosed with retinitis pigmentosa (RP). The compound heterozygous c.138delA (p.Asp47IlefsX24) and c.1841G>T (p.Gly614Val) mutations in the Crumbs homolog 1 (CRB1) gene were identified in all the affected patients but not in the unaffected individuals in this family. These mutations were inherited from their parents, respectively.CONCLUSIONThe novel compound heterozygous mutations in CRB1 were identified in a Chinese pedigree with ARRP using targeted-capture next generation sequencing. After evaluating the significant heredity and impaired protein function, the compound heterozygous c.138delA (p.Asp47IlefsX24) and c.1841G>T (p.Gly614Val) mutations are the causal genes of early onset ARRP in this pedigree. To the best of our knowledge, there is no previous report regarding the compound mutations.

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Retinal Dystrophy with Intraretinal Cystoid Spaces Associated with Mutations in the Crumbs Homologue (CRB1) Gene

Abstract: CRB1 mutations may be associated with intraretinal cystoid spaces. The use of carbonic anhydrase inhibitors can result in improved visual acuity in some patients.

Cited by 19 publications

References 48 publications

Rebound macular edema following oral acetazolamide therapy for juvenile X-linked retinoschisis in an Italian family

Rebound macular edema following oral acetazolamide therapy for juvenile X-linked retinoschisis in an Italian family

Phenotypic features of CRB1-associated early-onset severe retinal dystrophy and the different molecular approaches to identifying the disease-causing variants

Novel mutations in CRB1 gene identified in a chinese pedigree with retinitis pigmentosa by targeted capture and next generation sequencing

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