Pathogenic Variants in CEP290 or IQCB1 Cause Earlier-Onset Retinopathy in Senior-Loken Syndrome Compared to Those in INVS, NPHP3, or NPHP4

Wang, Junwen; Li, Shiqiang; Jiang, Y.; Wang, Yingwei; Ouyang, Jiamin; Yi, Zhen; Sun, Wenmin; Jia, Xiaoyun; Xiao, Xia; Wang, Panfeng; Zhang, Qingjiong

doi:10.1016/j.ajo.2023.03.025

Cited by 3 publications

(2 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ocular symptoms and signs in the four unrelated patients with biallelic FDXR variants met the criteria for a diagnosis of congenital amaurosis, especially at the early stage when the systemic signs and symptoms have not yet been developed or rarely recognized. Similarly, LCA with extraocular abnormalities has been well documented in systemic diseases, such as Senior-Loken syndrome in which LCA may be noticed in infancy while end-stage renal disease may be observed in teenage years [ 32 ]. For FDXR -associated congenital amaurosis, the triad fundus changes might be considered as gene-specific, including complete optic disc pallor, silver wiring of retinal vessels, and generalized retinal degeneration.…”

Section: Discussionmentioning

confidence: 99%

FDXR-Associated Oculopathy: Congenital Amaurosis and Early-Onset Severe Retinal Dystrophy as Common Presenting Features in a Chinese Population

Zheng

Zhen

et al. 2023

Genes

Self Cite

View full text Add to dashboard Cite

Variants in FDXR reportedly cause autosomal recessive auditory neuropathy and optic atrophy, expanding to retinal dystrophy. This study aimed to further clarify associated phenotypes. FDXR variants were selected from our in-house whole-exome sequencing dataset of 6397 families with different eye conditions. The clinical data of the identified patients were summarized. Biallelic pathogenic or likely pathogenic FDXR variants were identified in 11 unrelated patients, including 14 missense variants of which 10 were novel. Fundus observation showed complete optic disc pallor, silver wiring or severe attenuation of retinal vessels, and varying degrees of generalized retinal degeneration. Before the detection of FDXR variants, four patients were clinically diagnosed as congenital amaurosis due to the presence of nystagmus a few months after birth, while seven were diagnosed as early-onset severe retinal dystrophy due to the presence of nyctalopia and/or poor vision in early childhood. Biallelic FDXR variants are a frequent cause of congenital or early-onset severe retinal dystrophy, especially for patients with severe optic atrophy and retinal dystrophy in early childhood.

show abstract

Section: Discussionmentioning

confidence: 99%

FDXR-Associated Oculopathy: Congenital Amaurosis and Early-Onset Severe Retinal Dystrophy as Common Presenting Features in a Chinese Population

Zheng

Zhen

et al. 2023

Genes

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is suggested that systemic disorders should be taken into consideration when no ophthalmic genetic causes can be identified in patients exhibiting ocular symptoms resembling other types of retinopathies and in the absence of systemic manifestations. As the most important human sense, the initial detection of autoimmune retinopathy in APS1 through routine ophthalmic examinations may be an early warning sign before systemic abnormalities occur, similar to the early diagnosis of retinopathy in CEP290 -associated Senior–Loken syndrome, thus providing a window of time to treat a kidney disease ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

Retinopathy as an initial sign of hereditary immunological diseases: report of six families and challenges in eye clinic

Wang,

Jiang,

Wang

et al. 2023

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

IntroductionRetinal degenerative or inflammatory changes may occur with hereditary immunological disorders (HID) due to variants in approximately 20 genes. This study aimed to investigate if such retinopathy may present as an initial sign of immunological disorders in eye clinic.MethodsThe variants in the 20 genes were selected from in-house exome sequencing data from 10,530 individuals with different eye conditions. Potential pathogenic variants were assessed by multistep bioinformatic analysis. Pathogenic variants were defined according to the ACMG/AMP criteria and confirmed by Sanger sequencing, co-segregation analysis, and consistency with related phenotypes. Ocular clinical data were thoroughly reviewed, especially fundus changes.ResultsA total of seven pathogenic variants in four of the 20 genes were detected in six probands from six families, including three with hemizygous nonsense variants p.(Q308*), p.(Q416*), and p.(R550*) in MSN, one with homozygous nonsense variants p.(R257*) in AIRE, one with compound heterozygous nonsense variants p.(R176*) and p.(T902*) in LAMB2, and one with a known c.1222T>C (p.W408R) heterozygous variant in CBL. Ocular presentation, as the initial signs of the diseases, was mainly retinopathy mimicking other forms of hereditary retinal degeneration, including exudative vitreoretinopathy in the three patients with MSN variants or tapetoretinal degeneration in the other three patients. Neither extraocular symptoms nor extraocular manifestations were recorded at the time of visit to our eye clinic. However, of the 19 families in the literature with retinopathy caused by variants in these four genes, only one family with an AIRE homozygous variant had retinopathy as an initial symptom, while the other 18 families had systemic abnormalities that preceded retinopathy.DiscussionThis study, for the first time, identified six unrelated patients with retinopathy as their initial and only presenting sign of HID, contrary to the previous reports where retinopathy was the accompanying sign of systemic HID. Recognizing such phenotype of HID may facilitate the clinical care of these patients. Follow-up visits to such patients and additional studies are expected to validate and confirm our findings.

show abstract

Double Hyperautofluorescence Rings as a Sign of CFAP410-related Retinopathy

Li,

Wang,

Wang

et al. 2023

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Pathogenic Variants in CEP290 or IQCB1 Cause Earlier-Onset Retinopathy in Senior-Loken Syndrome Compared to Those in INVS, NPHP3, or NPHP4

Cited by 3 publications

References 64 publications

FDXR-Associated Oculopathy: Congenital Amaurosis and Early-Onset Severe Retinal Dystrophy as Common Presenting Features in a Chinese Population

FDXR-Associated Oculopathy: Congenital Amaurosis and Early-Onset Severe Retinal Dystrophy as Common Presenting Features in a Chinese Population

Retinopathy as an initial sign of hereditary immunological diseases: report of six families and challenges in eye clinic

Double Hyperautofluorescence Rings as a Sign of CFAP410-related Retinopathy

Contact Info

Product

Resources

About