Prevalence and genetic–phenotypic characteristics of patients with <i>USH2A</i> mutations in a large cohort of Chinese patients with inherited retinal disease

Gao, Feng‐Juan; Wang, Dandan; Chen, Fang; Sun, Hao-Xiang; Hu, Fangyuan; Xu, Ping; Li, Jiankang; Liu, Wei; Qi, Yu-He; Li, Wei; Wang, Ming; Zhang, Shenghai; Xu, Gezhi; Chang, Qing

doi:10.1136/bjophthalmol-2020-315878

Cited by 27 publications

(23 citation statements)

References 12 publications

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“…Multiple studies from different countries have recognized a USH2A allelic hierarchy, where truncating alleles are associated with the clinical diagnosis of USH2 and hearing loss, and several missense alleles are associated with a clinical diagnosis of ARRP (Gao et al, 2021; Hartel et al, 2016; Inaba et al, 2020; Lenassi et al, 2015; Meng et al, 2020; Molina‐Ramirez et al, 2020; Pierrache et al, 2016). The presence of specific missense alleles enriched in ARRP is associated with differences in age of onset and severity of retinal degeneration.…”

Section: Discussionmentioning

confidence: 99%

Tissue‐specific genotype–phenotype correlations among USH2A‐related disorders in the RUSH2A study

et al. 2022

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We assessed genotype–phenotype correlations among the visual, auditory, and olfactory phenotypes of 127 participants with Usher syndrome (USH2) (n =80) or nonsyndromic autosomal recessive retinitis pigmentosa (ARRP) (n = 47) due to USH2A variants, using clinical data and molecular diagnostics from the Rate of Progression in USH2A Related Retinal Degeneration (RUSH2A) study. USH2A truncating alleles were associated with USH2 and had a dose‐dependent effect on hearing loss severity with no effect on visual loss severity within the USH2 subgroup. A group of missense alleles in an interfibronectin domain appeared to be hypomorphic in ARRP. These alleles were associated with later age of onset, larger visual field area, better sensitivity thresholds, and better electroretinographic responses. No effect of genotype on the severity of olfactory deficits was observed. This study unveils a unique, tissue‐specific USH2A allelic hierarchy with important prognostic implications for patient counseling and treatment trial endpoints. These findings may inform clinical care or research approaches in others with allelic disorders or pleiotropic phenotypes.

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Section: Discussionmentioning

confidence: 99%

Tissue‐specific genotype–phenotype correlations among USH2A‐related disorders in the RUSH2A study

et al. 2022

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“…The gene USH2A located on chromosome 1q41, and codes for Usherin, a transmembrane protein present in the basement membrane of photoreceptor cells and hair cells of the cochlea, and which has an important role in the development and homeostasis of the inner ear and retina [3].…”

Section: Discussionmentioning

confidence: 99%

Usher Deafblindnes

Khamaily¹,

Bajjouk²,

Bouchaar³

et al. 2020

EJMED

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Pigmentary retinopathy refers to a group of inherited degenerative diseases of the retina, which primarily affects the photoreceptor cells in the retina. The association with congenital hearing loss defines Usher syndrome. Usher syndrome is a rare pathology of autosomal recessive transmission with a double sensory impairment (auditory and visual). We report the observation of a 12-year-old patient from a consanguineous marriage with congenital deafness, normal vestibular function and pigmentary retinopathy composing type 2 of Usher syndrome.

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“…Some disease-causing variants in the same genes can be associated with different disorders. For example, biallelic variants in USH2A can be associated with syndromic disorder such as type II USH or non-syndromic RP (202)(203)(204). Many of the monogenic recessive disease could be treated with vector-based gene replacement approach as mentioned previously, where the cDNA of the mutated gene is delivered to compensate for the lack of protein production.…”

Section: Autosomal Recessive Diseasementioning

confidence: 99%

Advancing precision medicines for ocular disorders: Diagnostic genomics to tailored therapies

et al. 2022

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Successful sequencing of the human genome and evolving functional knowledge of gene products has taken genomic medicine to the forefront, soon combining broadly with traditional diagnostics, therapeutics, and prognostics in patients. Recent years have witnessed an extraordinary leap in our understanding of ocular diseases and their respective genetic underpinnings. As we are entering the age of genomic medicine, rapid advances in genome sequencing, gene delivery, genome surgery, and computational genomics enable an ever-increasing capacity to provide a precise and robust diagnosis of diseases and the development of targeted treatment strategies. Inherited retinal diseases are a major source of blindness around the world where a large number of causative genes have been identified, paving the way for personalized diagnostics in the clinic. Developments in functional genetics and gene transfer techniques has also led to the first FDA approval of gene therapy for LCA, a childhood blindness. Many such retinal diseases are the focus of various clinical trials, making clinical diagnoses of retinal diseases, their underlying genetics and the studies of natural history important. Here, we review methodologies for identifying new genes and variants associated with various ocular disorders and the complexities associated with them. Thereafter we discuss briefly, various retinal diseases and the application of genomic technologies in their diagnosis. We also discuss the strategies, challenges, and potential of gene therapy for the treatment of inherited and acquired retinal diseases. Additionally, we discuss the translational aspects of gene therapy, the important vector types and considerations for human trials that may help advance personalized therapeutics in ophthalmology. Retinal disease research has led the application of precision diagnostics and precision therapies; therefore, this review provides a general understanding of the current status of precision medicine in ophthalmology.

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Prevalence and genetic–phenotypic characteristics of patients with USH2A mutations in a large cohort of Chinese patients with inherited retinal disease

Cited by 27 publications

References 12 publications

Tissue‐specific genotype–phenotype correlations among USH2A‐related disorders in the RUSH2A study

Tissue‐specific genotype–phenotype correlations among USH2A‐related disorders in the RUSH2A study

Usher Deafblindnes

Advancing precision medicines for ocular disorders: Diagnostic genomics to tailored therapies

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