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1.
Invest Ophthalmol Vis Sci ; 64(3): 23, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36912596

ABSTRACT

Purpose: To describe the phenotype of CLN-associated retinal dystrophy in a subset of patients at the Columbia University Medical Center, United States, and the Hospital das Clínicas de Pernambuco, Brazil, in comparison to the published literature. Methods: Eleven patients with confirmed biallelic variants in the CLN genes were evaluated via dilated fundus examination, clinical imaging, and full-field electroretinogram. A thorough literature search was conducted to determine previously published variants and associated phenotypes. Results: Genetic testing confirmed the presence of variants in CLN3, CLN7/MFSD8, CLN8, and GRN/CLN11. Five novel variants were identified, and four novel phenotypes of previously published alleles were described. The phenotype differed among patients with variants in the same gene and sometimes among patients with the same allele. Conclusions: Substantial phenotypic variability among variants in the CLN genes makes identification of genotype-phenotype or allele-phenotype correlations challenging. Further study is required to establish an extensive database for adequate patient counseling.


Subject(s)
Genetic Testing , Retinal Dystrophies , Humans , Mutation , Pedigree , Phenotype , Retinal Dystrophies/diagnosis , Retinal Dystrophies/genetics , Biological Variation, Population , Membrane Glycoproteins/genetics , Molecular Chaperones/genetics , Membrane Transport Proteins/genetics
2.
Doc Ophthalmol ; 146(3): 267-272, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36609934

ABSTRACT

INTRODUCTION: Mutations in the peripherin-2 gene (PRPH2) are a common cause of inherited retinal dystrophies well known for their phenotypic diversity. We describe a novel presentation of the c.623G > A; p.(Gly208Asp) variant in association with cone-rod dystrophy and reduced penetrance. CASE DESCRIPTION: A 39-year-old man presents with a history of decreased visual acuity, photophobia, and dyschromatopsia. Fundus examination was largely unremarkable while spectral-domain optical coherence tomography (SD-OCT) demonstrated diffuse granularity at the ellipsoid zone. Full-field electroretinogram (ffERG) revealed a cone-rod dystrophy. Genetic testing revealed a heterozygous pathogenic variant, c.623G > A; p.(Gly208Asp), in the PRPH2 gene, also found in an unaffected brother. The 50-year-old brother had no visual symptoms and no findings on fundus examination. SD-OCT showed normal retinal architecture and ffERG was within normal limits bilaterally. CONCLUSION: This case report broadens the known phenotypic presentations of PRPH2-associated retinopathy and suggests that the PRPH2 variant c.623G > A; p.(Gly208Asp) may be associated with reduced penetrance.


Subject(s)
Cone-Rod Dystrophies , Retinitis Pigmentosa , Male , Humans , Adult , Middle Aged , Cone-Rod Dystrophies/diagnosis , Cone-Rod Dystrophies/genetics , Penetrance , Electroretinography , Retinitis Pigmentosa/diagnosis , Retinitis Pigmentosa/genetics , Mutation , Biological Variation, Population , Tomography, Optical Coherence , Phenotype
3.
Methods Mol Biol ; 2560: 41-66, 2023.
Article in English | MEDLINE | ID: mdl-36481882

ABSTRACT

Retinitis pigmentosa (RP) affects approximately 1 in 4000 individuals. It has many different genetic etiologies and therefore diagnosis can be challenging. Understanding the different testing methodologies is beneficial for clinicians and researchers in order to select the best testing method, whether it be panel testing, whole exome sequencing, or whole genome sequencing for individuals affected with RP. The Methods section also outlines the steps required to complete a WES assay, which has become a popular method for identifying the molecular diagnosis for individuals with RP.


Subject(s)
Retinitis Pigmentosa , Humans , Retinitis Pigmentosa/diagnosis , Retinitis Pigmentosa/genetics , Molecular Biology
4.
Sci Rep ; 12(1): 9358, 2022 06 07.
Article in English | MEDLINE | ID: mdl-35672425

ABSTRACT

Inherited retinal degenerations are clinically and genetically heterogeneous diseases characterized by progressive deterioration of vision. This study aimed at assessing the diagnostic yield of exome sequencing (ES) for an unselected cohort of individuals with hereditary retinal disorders. It is a retrospective study of 357 unrelated affected individuals, diagnosed with retinal disorders who underwent clinical ES. Variants from ES were filtered, prioritized, and classified using the ACMG recommendations. Clinical diagnosis of the individuals included rod-cone dystrophy (60%), macular dystrophy (20%), cone-rod dystrophy (9%), cone dystrophy (4%) and other phenotypes (7%). Majority of the cases (74%) were singletons and 6% were trios. A confirmed molecular diagnosis was obtained in 24% of cases. In 6% of cases, two pathogenic variants were identified with phase unknown, bringing the potential molecular diagnostic rate to ~ 30%. Including the variants of uncertain significance (VUS), potentially significant findings were reported in 57% of cases. Among cases with a confirmed molecular diagnosis, variants in EYS, ABCA4, USH2A, KIZ, CERKL, DHDDS, PROM1, NR2E3, CNGB1, ABCC6, PRPH2, RHO, PRPF31, PRPF8, SNRNP200, RP1, CHM, RPGR were identified in more than one affected individual. Our results support the utility of clinical ES in the diagnosis of genetically heterogeneous retinal disorders.


Subject(s)
Cone-Rod Dystrophies , Retinal Dystrophies , ATP-Binding Cassette Transporters/genetics , Cell Cycle Proteins , Cone-Rod Dystrophies/diagnosis , Cone-Rod Dystrophies/genetics , Cyclic Nucleotide-Gated Cation Channels/genetics , DNA Mutational Analysis , Exome/genetics , Eye Proteins/genetics , Humans , Mutation , Pedigree , Phenotype , Retinal Dystrophies/diagnosis , Retinal Dystrophies/genetics , Retrospective Studies , Tertiary Care Centers
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