Dataset Information

Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature.

ABSTRACT:

Purpose

The purpose of this study was to report retinal dystrophy as a novel clinical feature and expand the ocular phenotype in patients harboring biallelic candidate FDXR variants.

Methods

Patients carrying biallelic candidate FDXR variants were identified by whole genome sequencing (WGS) as part of the National Institute for Health Research BioResource rare-disease and the UK's 100,000 Genomes Project (100KGP) with an additional case identified by exome sequencing. Retrospective clinical data were collected from the medical records. Haplotype reconstruction was performed in families harboring the same missense variant.

Results

Ten individuals from 8 unrelated families with biallelic candidate variants in FDXR were identified. In addition to bilateral optic atrophy and variable extra-ocular findings, 7 of 10 individuals manifested retinal dystrophy comprising dysfunction and degeneration of both rod and cone photoreceptors. Five of 10 subjects had sensorineural hearing loss. The previously unreported missense variant (c.1115C > A, p.(Pro372His)) was found in 5 of 8 (62.5%) study families. Haplotype reconstruction using WGS data demonstrated a likely ancestral haplotype.

Conclusions

FDXR-associated disease is a phenotypically heterogeneous disorder with retinal dystrophy being a major clinical feature observed in this cohort. In addition, we hypothesize that a number of factors are likely to drive the pathogenesis of optic atrophy, retinal degeneration, and perhaps the associated systemic manifestations.

SUBMITTER: Jurkute N

PROVIDER: S-EPMC8107637 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature.

Jurkute Neringa N Shanmugarajah Priya D PD Hadjivassiliou Marios M Higgs Jenny J Vojcic Miodrag M Horrocks Iain I Nadjar Yann Y Touitou Valerie V Lenaers Guy G Poh Roy R Acheson James J Robson Anthony G AG Raymond F Lucy FL Reilly Mary M MM Yu-Wai-Man Patrick P Moore Anthony T AT Webster Andrew R AR Arno Gavin G

Investigative ophthalmology & visual science 20210501 6

<h4>Purpose</h4>The purpose of this study was to report retinal dystrophy as a novel clinical feature and expand the ocular phenotype in patients harboring biallelic candidate FDXR variants.<h4>Methods</h4>Patients carrying biallelic candidate FDXR variants were identified by whole genome sequencing (WGS) as part of the National Institute for Health Research BioResource rare-disease and the UK's 100,000 Genomes Project (100KGP) with an additional case identified by exome sequencing. Retrospectiv ...[more]

PMID: 33938912

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Project description:Background Inherited retinal diseases (IRD) represent a prominent etiology of visual impairment on a global scale. The lack of a clear definition of the etiology and genotypic spectrum of IRD is attributed to the significant genetic variability seen. Additionally, there is a scarcity of available data about the correlations between genotypes and phenotypes in this context. This study aimed to clarify the range of mutations and the associations between genotypes and phenotypes in IRD. Methods This cohort consists of 223 patients who have been diagnosed with a range of retinal illnesses, such as retinitis pigmentosa (RP), Stargardt (STGD)/STGD-like disease, Usher syndrome, and Leber congenital amaurosis (LCA). The validation of each mutation and its pathogenicity was conducted by bioinformatics analysis, Sanger sequencing-based co-segregation testing, and computational assessment. The link between genotype and phenotype was analyzed in all patients who possessed mutations as described in the recommendations established by the American College of Medical Genetics. Results A total of 223 cases, comprising Turkish and Syrian families, were examined, revealing the presence of 175 distinct mutations in the IRD gene. Among these mutations, 58 were identified as unique, indicating that they had not been previously reported. A total of 119 mutations were identified to be likely pathogenic, while 104 mutations were classified as pathogenic. The study identified patterns of heredity, namely autosomal recessive, dominant, and X-linked inheritance. Conclusions The findings of this study broaden the clinical and molecular aspects of IRD and further enhance our understanding of its complex nature. The discovery of previously unknown relationships between genetic variations and observable traits, as well as the wide range of genetic variants associated with IRD, significantly contributes to our existing understanding of the diverse phenotypic and genotypic characteristics of IRD. This new information will prove invaluable in facilitating accurate clinical diagnoses as well as personalized therapeutic interventions for individuals affected by IRD.

Dataset Information

Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature.

Purpose

Methods

Results

Conclusions

Publications

Expanding the FDXR-Associated Disease Phenotype: Retinal Dystrophy Is a Recurrent Ocular Feature.

Similar Datasets

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