Punctiform and Polychromatic Pre-Descemet Corneal Dystrophy: Clinical Evaluation and Identification of the Genetic Basis
| Autor: | Vinay S. Swamy, Doug D Chung, Ana Boto-de-los-Bueis, Olena Al-Shymali, Jorge L. Alió del Barrio, Kavya Jatavallabhula, Anthony J. Aldave, Pilar Yébana, Jorge L. Alió, María Angélica Henríquez-Recine, Alice Barrington |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Peroxiredoxin III Corneal dystrophy Ophthalmology & Optometry medicine.disease_cause Whole Exome Sequencing Cornea 0302 clinical medicine Locus heterogeneity 2.1 Biological and endogenous factors Missense mutation Aetiology Child Tomography Exome sequencing Sanger sequencing Genetics Corneal Dystrophies Hereditary Microscopy 0303 health sciences Mutation Microscopy Confocal Middle Aged Phenotype Biomechanical Phenomena Pedigree Hereditary Confocal Public Health and Health Services symbols Female Tomography Optical Coherence Adult Corneal Dystrophies Adolescent Clinical Sciences Mutation Missense Biology Article 03 medical and health sciences symbols.namesake Young Adult Clinical Research Opthalmology and Optometry Anterior Eye Segment Exome Sequencing medicine Humans Eye Disease and Disorders of Vision 030304 developmental biology Aged Case-control study medicine.disease Ophthalmology Optical Coherence Case-Control Studies 030221 ophthalmology & optometry Missense |
| Zdroj: | Am J Ophthalmol |
| ISSN: | 1879-1891 |
| Popis: | PURPOSE: To report the clinical features and genetic basis of three previously unreported families with punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD). DESIGN: Observational case series. METHODS: Full ophthalmic assessment was performed for members of three unreported families with PPPCD. Structural and biomechanical alterations of the cornea were screened. Whole-exome-sequencing (WES) was performed on the first family. Novel or rare variants that segregated with the affected status were screened for in the other two families with Sanger sequencing. Identified variants that segregated with the affected status in all families were characterized using in silico prediction tools and/or in vitro splice assays. Additionally, two previously reported PPPCD families were screened for variants identified in the three unreported PPPCD families. RESULTS: Twelve of 21 examined members of the three unreported families were diagnosed with PPPCD. The only refractive, topographic or biomechanical abnormality associated with PPPCD was a significantly increased corneal stiffness. WES and Sanger sequencing identified two variants that segregated with the affected status in the all three families: a rare intronic PDZD8 c.872+10A>T variant and a novel missense PRDX3 c.568G>C (p.Asp190His) variant. The same PRDX3 variant was identified in the previously reported PPPCD family expressing the common PPPCD phenotype, and is predicted by in silico prediction tools to be damaging to protein function. CONCLUSIONS: PPPCD is associated with an alteration of corneal biomechanics and a novel missense variant in PRDX3. Screening of additional families will determine whether all families demonstrate a PRDX3 variant, or whether locus heterogeneity may exist for PPPCD. |
| Databáze: | OpenAIRE |
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