CRB1-Related Leber Congenital Amaurosis: Reporting Novel Pathogenic Variants and a Brief Review on Mutations Spectrum

Saberi, Mohammad Reza; Golchehre, Zahra; Karamzade, Arezou; Entezam, Mona; Eshaghkhani, Yeganeh; Alavinejad, Elaheh; Jafari, Hassan; Keramatipour, Mohammad

doi:10.29252/ibj.23.5.8

Cited by 8 publications

(4 citation statements)

References 43 publications

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“…In addition, CRB1 mutations are responsible for 3-9% of non-syndromic arRP cases [91]. Moreover, it was observed that 9-15% of LCA cases have mutations in CRB1 [93]. Recessive CRB1 mutations may also cause CRD with MD in childhood, with electronegative ERG [94].…”

Section: Crb1mentioning

confidence: 99%

A review of recent developments in retinitis pigmentosa genetics, its clinical features, and natural course

Loukovitis¹,

Anastasia²,

Tranos³

et al. 2021

Med Hypothesis Discov Innov Ophthalmol

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Background: Retinitis pigmentosa (RP), an inherited degenerative ocular disease, is considered the most common type of retinal dystrophy. Abnormalities of the photoreceptors, particularly the rods, and of the retinal pigment epithelium, characterizes this disease. The abnormalities progress from the midperiphery to the central retina. We here reviewed the developments in RP genetics in the last decade, along with its clinical features and natural course. Methods: The present review focused on articles in English language published between January 2008 and February 2020, and deposited in PubMed and Google Scholar databases. We searched for articles reporting on the clinical manifestations and genes related to both syndromic and non-syndromic RP. We screened and analyzed 139 articles, published in the last decade, referring to RP pathogenesis and identified, summarized, and highlighted the most significant genes implicated in either syndromic or non-syndromic RP pathogenesis, causing different clinical manifestations. Results: Recent literature revealed that approximately 80 genes are implicated in non-syndromic RP, and 30 genes in syndromic forms, such as Usher syndrome and Bardet‒Biedl syndrome (BBS). Moreover, it is estimated that 27 genes are implicated in autosomal dominant RP (adRP), 55 genes in autosomal recessive RP (arRP), and 6 genes in X-linked RP (xlRP), causing different RP phenotypes. Characteristically, RHO is the most prevalent adRP- and arRP-causing gene, and RPGR the most common xlRP-causing gene. Other important genes are PRPH2, RP1, CRX, RPE65, ABCA4, CRB1, and USH2Α. However, different phenotypes can also be caused by mutations in the same gene. Conclusions: The genetic heterogeneity of RP necessitates further study to map the exact mutations that cause more severe forms of RP, and to develop and use appropriate genetic or other effective therapies in future.

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Section: Crb1mentioning

confidence: 99%

A review of recent developments in retinitis pigmentosa genetics, its clinical features, and natural course

Loukovitis¹,

Anastasia²,

Tranos³

et al. 2021

Med Hypothesis Discov Innov Ophthalmol

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“…Additionally, CRB1 mutations account for 3% to 9% of non-syndromic arRP 50 and 9-15% of LCA cases. 51 Also, childhood CRD with macular cystic degeneration and autosomal dominant Stargardt disease phenotypes appear frequently. 52 However, clinical variability in patients with same CRB1 mutations indicates that arRP associated with CRB1 may also be modulated by other factors.…”

Section: Crb1 Genementioning

confidence: 99%

Recent Developments on the major genes involved in retinitis pigmentosa

A¹,

D²,

A³

et al. 2020

IJOOO

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Retinitis pigmentosa (RP) is a common retinal dystrophy that affects millions of individuals, of both sexes, worldwide. The age of onset and the phenotypic characteristics vary between patients of different ethnicities. It may be syndromic when it coexists with several syndromes, like Usher syndrome, or nonsyndromic. It follows autosomal dominant, autosomal recessive or X-linked inheritance. RP is genetically heterogeneous with, approximately, one hundred genes identified to date. The present mini review includes articles about the pathogenesis of syndromic and non-syndromic RP. Eighty-seven papers written in English and published in the last decade, about the pathogenesis of RP were reviewed and analyzed in order to summarize and highlight the major genes implicated in RP. We identified more than 80 genes associated with syndromic and 30 genes with non-syndromic RP. Among them RHO and RPGR, followed by PRPH2, PRPF31 and RP2 are the major genes involved in RP.

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“…This difference in disease severity may be attributed to LCA being due to defective retinal progenitor cells during early ocular development, while RCD is caused by faulty photoreceptor-muller cell interaction [ 3 ]. Previous reports show that 9 to 15% of LCA cases [ 4 ] and 6.5% [ 5 ] of RCD cases result from biallelic CRB1 mutations.…”

Section: Introductionmentioning

confidence: 99%

Genotype-phenotype associations in CRB1 bi-allelic patients: a novel mutation, a systematic review and meta-analysis

Daher,

Banjak,

Noureldine

et al. 2024

BMC Ophthalmol

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Purpose The goal of the study was to search for novel bi-allelic CRB1 mutations, and then to analyze the CRB1 literature at the genotypic and phenotypic levels. Approach We screened various variables such as the CRB1 mutation types, domains, exons, and genotypes and their relation with specific ocular phenotypes. An emphasis was given to the bi-allelic missense and nonsense mutations because of their high prevalence compared to other mutation types. Finally, we quantified the effect of various non-modifiable factors over the best-corrected visual acuity oculus uterque (BCVA OU) using multivariate linear regression models and identified genetic interactions. Results A novel bi-allelic missense in the exon 9 of CRB1; c.2936G > A; p.(Gly979Asp) was found to be associated with rod-cone dystrophy (RCD). CRB1 mutation type, exons, domains, and genotype distribution varied significantly according to fundus characteristics, such as peripheral pigmentation and condition, optic disc, vessels, macular condition, and pigmentation (P < 0.05). Of the 154 articles retrieved from PubMed, 96 studies with 439 bi-allelic CRB1 patients were included. Missense mutations were significantly associated with an absence of macular pigments, pale optic disc, and periphery pigmentation, resulting in a higher risk of RCD (P < 0.05). In contrast, homozygous nonsense mutations were associated with macular pigments, periphery pigments, and a high risk of LCA (P < 0.05) and increased BCVA OU levels. We found that age, mutation types, and inherited retinal diseases were critical determinants of BCVA OU as they significantly increased it by 33% 26%, and 38%, respectively (P < 0.05). Loss of function alleles additively increased the risk of LCA, with nonsense having a more profound effect than indels. Finally, our analysis showed that p.(Cys948Tyr) and p.(Lys801Ter) and p.(Lys801Ter); p.(Cys896Ter) might interact to modify BCVA OU levels. Conclusion This meta-analysis updated the literature and identified genotype-phenotype associations in bi-allelic CRB1 patients.

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CRB1-Related Leber Congenital Amaurosis: Reporting Novel Pathogenic Variants and a Brief Review on Mutations Spectrum

Cited by 8 publications

References 43 publications

A review of recent developments in retinitis pigmentosa genetics, its clinical features, and natural course

A review of recent developments in retinitis pigmentosa genetics, its clinical features, and natural course

Recent Developments on the major genes involved in retinitis pigmentosa

Genotype-phenotype associations in CRB1 bi-allelic patients: a novel mutation, a systematic review and meta-analysis

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