Syndromic and non-syndromic forms of retinitis pigmentosa: a comprehensive Italian clinical and molecular study reveals new mutations

Pierrottet, Chiara O.; Zuntini, Monia; Digiuni, Maurizio; Bazzanella, I.; Ferri, Paolo; Paderni, R.; Rossetti, Luca; Cecchin, Stefano; Orzalesi, N.; Bertelli, Matteo

doi:10.4238/2014.october.27.23

Cited by 29 publications

(16 citation statements)

References 35 publications

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“…The prevalence of IRD and most importantly the frequency of gene mutations causing those diseases are not well characterized in Italy and only few data have been reported [22–24]. RPE65, CRB1, and GUCY2D were identified as the most prevalent mutated genes in Italian LCA patients [22] and RHO was reported to be the gene most commonly responsible for ADRP [23] and EYS the most recurrent for nonsyndromic ARRP and sporadic cases [24].…”

Section: Discussionmentioning

confidence: 99%

“…RPE65, CRB1, and GUCY2D were identified as the most prevalent mutated genes in Italian LCA patients [22] and RHO was reported to be the gene most commonly responsible for ADRP [23] and EYS the most recurrent for nonsyndromic ARRP and sporadic cases [24]. Our study contributes only partially to the knowledge of the gene mutation frequencies, since each IRD type is represented by small cohorts of cases (i.e., the LCA and dominant RP phenotypes were accounted for by 5 and 6 cases, resp.…”

Section: Discussionmentioning

confidence: 99%

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Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

Bernardis

Chiesi

Tenedini

et al. 2016

BioMed Research International

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To assess the clinical utility of targeted Next-Generation Sequencing (NGS) for the diagnosis of Inherited Retinal Dystrophies (IRDs), a total of 109 subjects were enrolled in the study, including 88 IRD affected probands and 21 healthy relatives. Clinical diagnoses included Retinitis Pigmentosa (RP), Leber Congenital Amaurosis (LCA), Stargardt Disease (STGD), Best Macular Dystrophy (BMD), Usher Syndrome (USH), and other IRDs with undefined clinical diagnosis. Participants underwent a complete ophthalmologic examination followed by genetic counseling. A custom AmpliSeq™ panel of 72 IRD-related genes was designed for the analysis and tested using Ion semiconductor Next-Generation Sequencing (NGS). Potential disease-causing mutations were identified in 59.1% of probands, comprising mutations in 16 genes. The highest diagnostic yields were achieved for BMD, LCA, USH, and STGD patients, whereas RP confirmed its high genetic heterogeneity. Causative mutations were identified in 17.6% of probands with undefined diagnosis. Revision of the initial diagnosis was performed for 9.6% of genetically diagnosed patients. This study demonstrates that NGS represents a comprehensive cost-effective approach for IRDs molecular diagnosis. The identification of the genetic alterations underlying the phenotype enabled the clinicians to achieve a more accurate diagnosis. The results emphasize the importance of molecular diagnosis coupled with clinic information to unravel the extensive phenotypic heterogeneity of these diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

Bernardis

Chiesi

Tenedini

et al. 2016

BioMed Research International

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“…The total absence of CERKL patients and the relatively small number of EYS patients in this paediatric cohort most likely reflects the typical adolescence or adult onset of those diseases (Pierrottet et al. , and Avela et al. ).…”

Section: Discussionmentioning

confidence: 94%

The genetic aetiology of retinal degeneration in children in Finland – new founder mutations identified

Avela

Salonen‐Kajander

Laitinen

et al. 2019

Acta Ophthalmologica

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Purpose: To study the genetic aetiology and phenotypes of retinal degeneration (RD) in Finnish children born during 1993-2009. Methods: Children with retinal degeneration (N = 68) were investigated during 2012-2014 with a targeted gene analysis or a next-generation sequencing (NGS) based gene panel. Also, a full clinical ophthalmological examination was performed. Results: The cohort covered 44% (68/153) of the Finnish children with inherited RD born 1993-2009. X-linked retinoschisis, retinitis pigmentosa, Leber congenital amaurosis and cone-rod dystrophy were the most common clinical diagnoses in the study group. Pathogenic mutations were found in 17 retinal genes. The molecular genetic aetiology was identified in 77% of the patients (in 77% of the families) analysed by NGS method. Several founder mutations were detected including three novel founder mutations c.148delG in TULP1, c.2314C>R (p.Gln772Ter) in RPGRIP1 and c.533G>A (Trp178Ter) in TYR. We also confirmed the previous tentative finding of c.2944 + 1delG in GYCU2D being the most frequent cause of Leber congenital amaurosis (LCA) in Finland. Conclusions: Globally, RD is genetically heterogeneous with over 260 disease genes reported so far. This was shown not to be the case in Finland, where the genetic aetiology of RD is caused by a small group of genes, due to several founder mutations that are enriched in the population. We found that Xchromosomal retinoschisis constitutes the major group in Finnish paediatric RD population and is almost exclusively caused by two founder mutations. Several other founder mutations were detected including three novel founder mutations. All in all, the genetic aetiology of 77% of families was identified which is higher than previously reported from other populations, likely due to the specific genomic constitution of the Finns.

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“…RP is classified as nonsyndromic (70%-80%) (14,15), syndromic or systemic (4,16). The most frequent form of syndromic RP is Usher syndrome (14,17) which involves neurosensory hearing loss, and Bardet-Biedl syndrome (18,19) which involves RP, obesity, renal abnormalities and mental retardation.…”

Section: Introductionmentioning

confidence: 99%

In silico analysis ofIDH3Agene revealed Novel mutations associated with Retinitis Pigmentosa

Mahmoud¹,

Abdelmoneim²,

Murshed³

et al. 2019

Preprint

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Background: Retinitis Pigmentosa (RP) refers to a group of inherited disorders characterized by the death of photoreceptor cells leading to blindness. The aim of this study is to identify the pathogenic SNPs in the IDH3A gene and their effect on the structure and function of the protein. Method: we used different bioinformatics tools to predict the effect of each SNP on the structure and function of the protein. Result: 20 deleterious SNPs out of 178 were found to have a damaging effect on the protein structure and function. Conclusion: this is the first in silico analysis of IDH3A gene and 20 novel mutations were found using different bioinformatics tools, and they could be used as diagnostic markers for Retinitis Pigmentosa.Keywords: Retinitis Pigmentosa (RP), IDH3A, SNP, in silico analysis, diagnostic markers.RP has three patterns of inheritance; autosomal dominant (adRP), autosomal recessive (arRP) and X-linked pattern (14,(20)(21)(22) and the most reported genes for each case are RHO gene, USH2A and RPGR respectively (4, 21-24) yet the gene we are working on, Isocitrate Dehydrogease 3, (IDH3A) is a novel gene identified as the cause of typical arRP (25) located in the human chromosome 15q25.1 (26). The IDH3A function is to catalyze the oxidative decarboxylation of isocitrate (27) which is the key rate-limiting step of the tricarboxylic acid cycle. It also plays a central role in the aerobic energy production and cellular respiration thus mutations in this gene will affect the nervous system (28, 29) and may cause cancer (30,31).Although the RP is the most common inherited disease of the retina (14, 32-36) there is still no effective therapeutic strategy and the exact pathogenesis and etiology of the disease is not clear (3,5,32,37).The aim of this study is to identify the pathogenic SNPs in the IDH3A gene and their effect on the structure and function of the protein, which might help in the overall understanding of the pathogenesis of the disease and could be used as diagnostic markers. This is the first in silico analysis in the coding region of IDH3A gene to prioritize SNPs for further genetic mapping studies. Utilization of in analysis softwares expedites the process of identifying the deleterious SNPs with no cost, and also facilitates future genetic studies. (38)

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Syndromic and non-syndromic forms of retinitis pigmentosa: a comprehensive Italian clinical and molecular study reveals new mutations

Cited by 29 publications

References 35 publications

Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

The genetic aetiology of retinal degeneration in children in Finland – new founder mutations identified

In silico analysis ofIDH3Agene revealed Novel mutations associated with Retinitis Pigmentosa

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