Genes and Mutations in Autosomal Dominant Cone and Cone-Rod Dystrophy

Kohl, Susanne; Kitiratschky, Veronique; Papke, Monika; Schaich, Simone; Sauer, Alexandra; Wissinger, Bernd

doi:10.1007/978-1-4614-0631-0_44

Cited by 21 publications

(15 citation statements)

References 22 publications

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“…24 A recent study conducted on a cohort of 52 patients and families with AD CD/CRD from Europe and the United States revealed 12 patients (23%) with mutations in the GUCY2D gene. 23 To our knowledge, this is the first report associating GUCY2D variants with AD cone phenotypes in the Israeli population, and the incidence (5 of 26 AD families, 19%) is similar to that observed in the aforementioned study. This finding is in contrast to what has been reported for AR roddominated retinal disease (RP and LCA) in Israel, in which causative genes and mutations largely differ from those reported in other populations.…”

Section: Discussionsupporting

confidence: 83%

“…To date, at least 10 genes associated with AD CD and CRD have been identified (RetNet), and mutations in GUCY2D were shown to be a major cause of AD cone disease in different ethnic groups worldwide, 23 with CD as the predominant phenotype. 24 A recent study conducted on a cohort of 52 patients and families with AD CD/CRD from Europe and the United States revealed 12 patients (23%) with mutations in the GUCY2D gene.…”

Section: Discussionmentioning

confidence: 99%

“…Amino acid position 838 is thought to be particularly prone to mutational changes due to the high number of cases observed in various ethnic backgrounds and is referred to as a mutation hotspot. 13,18,23,[28][29][30][31] Functional analysis of the mutant retinal guanylate cyclase at position 838 revealed a change in affinity toward regulation by calcium-bound inhibiting and calcium-free activating forms of the guanylate cyclase activating protein. 26 The disease is thought to result from an imbalance of cGMP and calcium in the photoreceptors.…”

Section: Discussionmentioning

confidence: 99%

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Whole Exome Sequencing Reveals GUCY2D as a Major Gene Associated With Cone and Cone-Rod Dystrophy in Israel

Lazar¹,

Mutsuddi²,

Kimchi³

et al. 2014

Investigative Ophthalmology & Visual Science

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Our study suggested that GUCY2D is a major cause of autosomal dominant cone and cone-rod dystrophies in Israel; this is similar to other Caucasian populations and is in contrast with retinitis pigmentosa (primary rod disease), where the genetic make-up of the Israeli population is distinct from other ethnic groups. We also conclude that WES permits more comprehensive and rapid analyses that can be followed by targeted screens of larger samples to delineate the genetic structure of retinal disease in unique population cohorts.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Whole Exome Sequencing Reveals GUCY2D as a Major Gene Associated With Cone and Cone-Rod Dystrophy in Israel

Lazar¹,

Mutsuddi²,

Kimchi³

et al. 2014

Investigative Ophthalmology & Visual Science

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“…Sanger sequencing of German families with 10 ad CCRD found similar results with GUCY2D mutations in 25 % of cases [68]. In the same study, prevalence of CRX and PROM1 were low (4 % and 2 % respectively) compared with our results (2/17 for PROM1 , 4/17 for CRX , 11.7 % and 23.5 %, respectively).…”

Section: Discussionsupporting

confidence: 82%

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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“…Sanger sequencing of 10 adCORD-associated genes identified mutations in 25 of 52 (48%) German families with adCORD, and mutations were found in GUCY2D (24%), PRPH2 (12%), GUCA1A (8%), CRX (4%), and PROM1 (2%) [43]. In other studies for individual genes, mutations in CRX are responsible for a 4.76% proportion of CORD [26], GUCY2D for 11.11% of CORD in a Japanese population [44] and 9.09% in a Spanish one [45], GUCA1A for 16.67% of CORD in a German one [46], PRPH2 for 11% of CORD in another German population [43], AIPL1 for 1.82% of CORD in an American sample [1], PROM1 for 0.93% of CORD in a Dutch population [16], SEMA4A for 8.00% of CORD in a Pakistani group [9], and UNC119 for 5.00% of CORD in another American population [10].…”

Section: Discussionmentioning

confidence: 99%

Exome Sequencing of 47 Chinese Families with Cone-Rod Dystrophy: Mutations in 25 Known Causative Genes

Huang

Zhang

et al. 2013

PLoS ONE

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ObjectiveThe goal of this study was to identify mutations in 25 known causative genes in 47 unrelated Chinese families with cone-rod dystrophy (CORD).MethodsForty-seven probands from unrelated families with CORD were recruited. Genomic DNA prepared from leukocytes was analyzed by whole exome sequencing. Variants in the 25 genes were selected and then validated by Sanger sequencing.ResultsFourteen potential pathogenic mutations, including nine novel and five known, were identified in 10 of the 47 families (21.28%). Homozygous, compound heterozygous, and hemizygous mutations were detected in three, four, or three families, respectively. The 14 mutations in the 10 families were distributed among CNGB3 (three families), PDE6C (two families), ABCA4 (one family), RPGRIP1 (one family), RPGR (two families), and CACNA1F (one family).ConclusionsThis study provides a brief view on mutation spectrum of the 25 genes in a Chinese cohort with CORD. Identification of novel mutations enriched our understanding of variations in these genes and their associated phenotypes. To our knowledge, this is the first systemic exome-sequencing analysis of all of the 25 CORD-associated genes.

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Genes and Mutations in Autosomal Dominant Cone and Cone-Rod Dystrophy

Cited by 21 publications

References 22 publications

Whole Exome Sequencing Reveals GUCY2D as a Major Gene Associated With Cone and Cone-Rod Dystrophy in Israel

Whole Exome Sequencing Reveals GUCY2D as a Major Gene Associated With Cone and Cone-Rod Dystrophy in Israel

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

Exome Sequencing of 47 Chinese Families with Cone-Rod Dystrophy: Mutations in 25 Known Causative Genes

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