Phenotypic characterization of a Chinese family with autosomal dominant cone–rod dystrophy related to GUCY2D

Xu, Fei; Fang, Dong; Li, Hui; Li, Xin; Jiang, Ruxin; Sui, Ruifang

doi:10.1007/s10633-013-9383-0

Cited by 7 publications

(3 citation statements)

References 20 publications

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“…Several reports have described patients with COD/CORD showing a coloboma-like macular atrophy caused by pathogenic variants in several genes, such as NMNAT1, 51,52 ADAM9, 53 GUCA1A, 54 and GUCY2D. 55 In the present study, an intrachoroidal cavitation resembling coloboma-like macular atrophy was presented in three subjects bilaterally or unilaterally. Poor visual acuity was observed in the eyes with intrachoroidal cavitation; thus, this striking finding implies severe central visual loss.…”

Section: Discussionsupporting

confidence: 57%

Clinical and Genetic Characteristics of 15 Affected Patients From 12 Japanese Families with GUCY2D-Associated Retinal Disorder

Liu

Fujinami

Kuniyoshi

et al. 2020

Trans. Vis. Sci. Tech.

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To determine the clinical and genetic characteristics of patients with GUCY2Dassociated retinal disorder (GUCY2D-RD). Methods: Fifteen patients from 12 families with inherited retinal disorder (IRD) and harboring GUCY2D variants were ascertained from 730 Japanese families with IRD. Comprehensive ophthalmological examinations, including visual acuity (VA) measurement, retinal imaging, and electrophysiological assessment were performed to classify patients into three phenotype subgroups; macular dystrophy (MD), cone-rod dystrophy (CORD), and Leber congenital amaurosis (LCA). In silico analysis was performed for the detected variants, and the molecularly confirmed inheritance pattern was determined (autosomal dominant/recessive [AD/AR]). Results: The median age of onset/examination was 22.0/38.0 years (ranges, 0-55 and 1-73) with a median VA of 0.80/0.70 LogMAR units (ranges, 0.00-1.52 and 0.10-1.52) in the right/left eye, respectively. Macular atrophy was identified in seven patients (46.7%), and two had diffuse fundus disturbance (13.3%), and six had an essentially normal

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Section: Discussionsupporting

confidence: 57%

Clinical and Genetic Characteristics of 15 Affected Patients From 12 Japanese Families with GUCY2D-Associated Retinal Disorder

Liu

Fujinami

Kuniyoshi

et al. 2020

Trans. Vis. Sci. Tech.

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“…Of the few well-described, detectable full-field ERGs that have been published, most shared the features described in this report, including a dark-adapted combined/maximal response that has an a-wave that is substantially reduced in proportion to the b-wave 26,41,42. It might be predicted that marked cone dysfunction in conjunction with a loss of rod sensitivity would produce this ERG phenotype in diffuse photoreceptor degenerations (CRD and RP)43,44; however, a review of the literature for ERG waveforms in at least 16 genetic forms of nonsyndromic CRD did not find this proportionally small a-wave to be present in a notable majority of published cases 11,27,28,34,35,37,42,45–54. Among the reviewed CRD cases, only a single CNGA3 -associated CRD and six related individuals with RDH12 -associated CRD were reported to have proportionally small a-waves with a dark-adapted combined response stimulus 15,55.…”

Section: Discussionsupporting

confidence: 53%

Characteristic Ocular Features in Cases of Autosomal Recessive PROM1 Cone-Rod Dystrophy

Collison¹,

Fishman

Nagasaki

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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Purpose To define characteristic ocular features in a group of patients with autosomal recessive (AR) PROM1 cone-rod dystrophy (CRD). Methods Three males and one female from three unrelated families were first seen at the ages of 15 to 22 years and diagnosed with CRD. Clinical testing available for review included full-field electroretinogram (ERG) in three patients, as well as near-infrared autofluorescence (NIR-AF), spectral-domain optical coherence tomography (SD-OCT), and color fundus photography in all four patients. Whole exome sequencing (WES) was performed on all cases, and whole genome sequencing (WGS) was performed in two families. Results WES found compound heterozygous PROM1 variants in one isolated male, plus heterozygous variants in the remaining patients. WGS uncovered deleterious PROM1 variants in these two families. ERG showed markedly reduced cone-isolated amplitudes and variably reduced rod-isolated amplitudes. The dark-adapted combined rod and cone responses demonstrated notably reduced a-wave amplitudes and moderately reduced b-waves, and the resultant waveform resembled the normal rod-isolated response. On fundus examination, oval-shaped macular lesions were observed, as were several small, circular hypoautofluorescent lesions within the posterior pole on NIR-AF. Three patients showed extramacular circular atrophic lesions. Conclusions The autofluorescence changes, peripheral retinal abnormalities, and ERG findings have not been emphasized in previous reports of AR PROM1 , but they became a recognizable phenotype in this cohort of patients. A similar constellation of findings may be observed in CRD due to CDHR1, a functionally related gene. The pattern of abnormalities reported herein may help to focus genetic screening in patients with these findings.

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“…One variant found within GUCY2D gene, c.2513G>C, is already known to cause an autosomal dominant form of cone-rod dystrophy [46][47][48]. The combination of this variant with the c.3044-7G>T, also in GUCY2D, might enforce the effects of GUCY2D mutated form.…”

Section: Discussionmentioning

confidence: 99%

The impact of modifier genes on cone-rod dystrophy heterogeneity: An explorative familial pilot study and a hypothesis on neurotransmission impairment

et al. 2022

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Cone-rod dystrophies (CORDs) are a heterogeneous group of inherited retinopathies (IRDs) with more than 30 already known disease-causing genes. Uncertain phenotypes and extended range of intra- and interfamilial heterogenicity make still difficult to determine a precise genotype-phenotype correlation. Here, we used a next-generation sequencing approach to study a Sicilian family with a suspected form of CORD. Affected family members underwent ophthalmological examinations and a proband, blind from 50 years, underwent whole genome and exome sequencing. Variant analysis was enriched by pathway analysis and relevant variants were, then, investigated in other family members and in 100 healthy controls from Messina. CORD diagnosis with an intricate pattern of symptoms was confirmed by ophthalmological examinations. A total of about 50,000 variants were identified in both proband’s genome and exome. All affected family members presented specific genotypes mainly determined by mutated GUCY2D gene, and different phenotypical traits, mainly related to focus and color perception. Thus, we looked for possible modifier genes. According to relationship with GUCY2D, predicted functional effects, eye localization, and ocular disease affinity, only 9 variants, carried by 6 genes (CACNG8, PAX2, RXRG, CCDC175, PDE4DIP and LTF), survived the filtering. These genes encode key proteins involved in cone development and survival, and retina neurotransmission. Among analyzed variants, CACNG8c.*6819A>T and the new CCDC175 c.76C>T showed extremely low frequency in the control group, suggesting a key role on disease phenotypes. Such discovery could enforce the role of modifier genes into CORD onset/progression, contributing to improve diagnostic test towards a better personalized medicine.

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Phenotypic characterization of a Chinese family with autosomal dominant cone–rod dystrophy related to GUCY2D

Abstract: A missense mutation in the GUCY2D gene caused ADCRD in this family. Clinical follow-up of this family with a typical CRD phenotype revealed disease progression during the time period.

Cited by 7 publications

References 20 publications

Clinical and Genetic Characteristics of 15 Affected Patients From 12 Japanese Families with GUCY2D-Associated Retinal Disorder

Clinical and Genetic Characteristics of 15 Affected Patients From 12 Japanese Families with GUCY2D-Associated Retinal Disorder

Characteristic Ocular Features in Cases of Autosomal Recessive PROM1 Cone-Rod Dystrophy

The impact of modifier genes on cone-rod dystrophy heterogeneity: An explorative familial pilot study and a hypothesis on neurotransmission impairment

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