Ocular findings associated with FADD deficiency resemble familial exudative vitreoretinopathy.
Ontology highlight
ABSTRACT: Purpose
We report the first known case of eye findings associated with a Fas-associated protein with death domain (FADD) gene mutation, an exceedingly rare entity.Observations
A 7-year-old boy was referred for decreased vision and eye examination revealed cystoid macular edema and peripheral retinal ischemia in both eyes and progression to tractional retinal detachment in the right eye.Conclusions and importance
This case suggests that baseline and annual ophthalmic screening may be beneficial in individuals with FADD mutations. However, greater documentation of cases may be necessary before deriving a clear interval screening recommendation.
SUBMITTER: Meer E
PROVIDER: S-EPMC8859737 | biostudies-literature | 2022 Mar
REPOSITORIES: biostudies-literature
Publications
Ocular findings associated with FADD deficiency resemble familial exudative vitreoretinopathy.
Meer Elana E Solanes Federica F Kohn Lisa L Kuo Caroline Y CY Wong Derek A DA Pineles Stacy S Tsui Irena I
American journal of ophthalmology case reports 20220203
<h4>Purpose</h4>We report the first known case of eye findings associated with a Fas-associated protein with death domain (FADD) gene mutation, an exceedingly rare entity.<h4>Observations</h4>A 7-year-old boy was referred for decreased vision and eye examination revealed cystoid macular edema and peripheral retinal ischemia in both eyes and progression to tractional retinal detachment in the right eye.<h4>Conclusions and importance</h4>This case suggests that baseline and annual ophthalmic scree ...[more]
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Project description:PurposeTo investigate the clinical findings in Chinese patients diagnosed with familial exudative vitreoretinopathy (FEVR) and carrying pathogenic mutations.MethodsOne hundred twenty unrelated patients with FEVR were enrolled in this study. Genomic DNA and ophthalmic examinations were collected from all the patients and their available relatives. Targeted next-generation sequencing was performed to detect mutations. In silico programs were used to evaluate the pathogenicity of all the mutations.ResultsEighty identified mutations were found in 81 unrelated patients (31/81 in LRP5, 25/81 in FZD4, 12/81 in TSPAN12, 8/81 in NDP, 4/81 in KIF11, and 1/81 in ZNF408). Among those mutations, 53 were novel (23/35 in LRP5, 15/21 in FZD4, 8/11 in TSPAN12, 3/8 in NDP, 3/4 in KIF11, 1/1 in ZNF408). Patients with LRP5, FZD4, TSPAN12, or NDP mutations were mainly classified into stage 4 and stage 5 and one-half of patients with KIF11 mutations were in stage 4. In addition, all the patients in NDP group were found to have bilateral symmetry in FEVR stage.ConclusionsOur results present profound phenotypic variability and a wide mutation spectrum of FEVR in the Chinese population, which could be useful for a precise and comprehensive genetic diagnosis for patients with FEVR in the future.
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Project description:Familial exudative vitreoretinopathy (FEVR) is a rare inherited disorder of retinal angiogenesis. Cases can be autosomal dominant, autosomal recessive, or X-linked. FEVR patients have an avascular peripheral retina which, depending on the degree of ischaemia, causes the secondary complications of the disease. Expressivity may be asymmetric and is highly variable. Five genes have been identified that when mutated, cause FEVR; NDP (X-linked), FZD4 (autosomal dominant and recessive), LRP5 (autosomal dominant and recessive), TSPAN12 (autosomal dominant and recessive), and ZNF408 (autosomal dominant). Four of these genes have been shown to have a central role in Norrin/Frizzled4 signalling, suggesting a critical role for this pathway in retinal angiogenesis. In addition to the ocular features, LRP5 mutations can cause osteopenia and osteoporosis. All FEVR patients in whom molecular testing is not easily accessible should have dual energy X-ray absorptiometry (DEXA) scans to assess bone mineral density, as treatment can be initiated to reduce the risk of bone fractures.
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Project description:Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder that affects both the retina and vitreous body. Autosomal recessive FEVR was diagnosed in multiple individuals from three consanguineous families of European descent. A candidate-locus-directed genome scan shows linkage to the region on chromosome 11q flanked by markers D11S905 and D11S1314. The maximum LOD score of 3.6 at theta =0 is obtained with marker D11S987. Haplotype analysis confirms that the critical region is the 22-cM (311-Mb) interval flanked by markers D11S905 and D11S1314. This region contains LRP5 but not FZD4; mutations in both of these genes cause autosomal dominant FEVR. Sequencing of LRP5 shows, in all three families, homozygous mutations R570Q, R752G, and E1367K. This suggests that mutations in this gene can cause autosomal recessive as well as autosomal dominant FEVR.
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