A Heterozygous Putative Null Mutation in ROM1 without a Mutation in Peripherin/RDS in a Family with Retinitis Pigmentosa

Sakuma, Hitoshi; Inana, George; Murakami, Akira; Yajima, Toshihiro; Weleber, Richard G.; Murphey, William H.; Gass, J. Donald M.; Hotta, Yoshihiro; Hayakawa, Mutsuko; Fujiki, Keiko; Gao, Yong; Danciger, Michael; Farber, Debora B.; Cideciyan, Artur V.; Jacobson, Samuel G.

doi:10.1006/geno.1995.1066

Cited by 31 publications

(9 citation statements)

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“…This gene was initially reported in digenic RP with PRPH2 mutation [78] and then implicated in a family with monogenic RP (c.339dupG p.(L114Afs*18)) [79]. However pathogenicity of mutations in ROM1 is still a matter of debate.…”

Section: Discussionmentioning

confidence: 99%

Next-generation sequencing applied to a large French cone and cone-rod dystrophy cohort: mutation spectrum and new genotype-phenotype correlation

Boulanger-Scemama

Shamieh

Démontant

et al. 2015

Orphanet J Rare Dis

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BackgroundCone and cone-rod dystrophies are clinically and genetically heterogeneous inherited retinal disorders with predominant cone impairment. They should be distinguished from the more common group of rod-cone dystrophies (retinitis pigmentosa) due to their more severe visual prognosis with early central vision loss. The purpose of our study was to document mutation spectrum of a large French cohort of cone and cone-rod dystrophies.MethodsWe applied Next-Generation Sequencing targeting a panel of 123 genes implicated in retinal diseases to 96 patients. A systematic filtering approach was used to identify likely disease causing variants, subsequently confirmed by Sanger sequencing and co-segregation analysis when possible.ResultsOverall, the likely causative mutations were detected in 62.1 % of cases, revealing 33 known and 35 novel mutations. This rate was higher for autosomal dominant (100 %) than autosomal recessive cases (53.8 %). Mutations in ABCA4 and GUCY2D were responsible for 19.2 % and 29.4 % of resolved cases with recessive and dominant inheritance, respectively. Furthermore, unexpected genotype-phenotype correlations were identified, confirming the complexity of inherited retinal disorders with phenotypic overlap between cone-rod dystrophies and other retinal diseases.ConclusionsIn summary, this time-efficient approach allowed mutation detection in the most important cohort of cone-rod dystrophies investigated so far covering the largest number of genes. Association of known gene defects with novel phenotypes and mode of inheritance were established.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-015-0300-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Next-generation sequencing applied to a large French cone and cone-rod dystrophy cohort: mutation spectrum and new genotype-phenotype correlation

Boulanger-Scemama

Shamieh

Démontant

et al. 2015

Orphanet J Rare Dis

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“…Clones from our human retinal cDNA library [8] were used to construct the interactive trap cDNA library (prey library) for the yeast two‐hybrid strategy. A number of important retina‐specific and ‐enriched clones has been isolated from this library, indicating the suitability of this library for construction of the prey library [1,8,10–12]. 80 000 primary clones were obtained in the prey library with an average insert size of 1.7 kb.…”

Section: Resultsmentioning

confidence: 90%

Photoreceptor synaptic protein HRG4 (UNC119) interacts with ARL2 via a putative conserved domain

et al. 2002

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Human retinal gene 4 (HRG4) (UNC119) is a photoreceptor synaptic protein of unknown function, shown when mutated to cause retinal degeneration in a patient and in a con¢rmatory transgenic model. ADP-ribosylation factor-like protein 2 (ARL2) was identi¢ed as an interactor of HRG4 by the yeast two-hybrid strategy. The presence of ARL2 in the retina and co-localization with HRG4 was con¢rmed by Western blot and double immuno£uorescence analysis, respectively. The interaction of ARL2 with HRG4 was further con¢rmed by co-immunoprecipitation and direct binding analysis. Phosphodiesterase N N (PDEN N) is an ARL2-binding protein homologous to HRG4. Amino acid residues of PDEN N involved in binding ARL2 and forming a hydrophobic pocket were shown to be highly conserved in HRG4, suggesting similarity in binding mechanism and function.

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“…One study on the digenic form of RP demonstrated that this p.L114Afs*18 mutation in ROM1 was a null mutation and only when combined with the p.L185P mutation in PRPH2 in double heterozygous state could cause RP (3). The mutation was also reported in adRP with different disease severities, and even when asymptomatic may be due to penetrance and expressivity of the disease or other reasons (16)(17)(18). It was detected in a patient with adRP and 2 out of 240 normal subjects in another study, which indicated that the mutation was not the causative mutation for the patient (18).…”

Section: Candidate Mutations In the Probandmentioning

confidence: 93%

Identification of a Disease-Causing Mutation in a Chinese Patient with Retinitis Pigmentosa by Targeted Next-Generation Sequencing

Xiao

Guo²,

Wang³

et al. 2017

European Journal of Ophthalmology

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A Heterozygous Putative Null Mutation in ROM1 without a Mutation in Peripherin/RDS in a Family with Retinitis Pigmentosa

Cited by 31 publications

References 0 publications

Next-generation sequencing applied to a large French cone and cone-rod dystrophy cohort: mutation spectrum and new genotype-phenotype correlation

Next-generation sequencing applied to a large French cone and cone-rod dystrophy cohort: mutation spectrum and new genotype-phenotype correlation

Photoreceptor synaptic protein HRG4 (UNC119) interacts with ARL2 via a putative conserved domain

Identification of a Disease-Causing Mutation in a Chinese Patient with Retinitis Pigmentosa by Targeted Next-Generation Sequencing

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