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Marcela Paz Perez Araya, Ajoy Vincent, Carol A Westall, Thomas Wright, Heather Trang, Chelsea Roadhouse, Elise Heon; Phenotypic variability of retinal degeneration within a consanguineous family. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1783. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To characterize the genotype(s) of individuals from a highly consanguineous family of Iraqi descent, affected with a range of retinal dystrophy phenotypes.
Eight members of a two generation family with vision loss (5 affected) underwent detailed ophthalmological evaluation, including best corrected visual acuity (BCVA; n=7), color vision (n=5) and contrast senstivity (n=5) measurements. All family members had fundus imaging, fundus auto-fluorescence testing (FAF) and spectral-domain optical coherence tomography (SD-OCT). All affected cases underwent full-field electroretinography (ERG). Commercially available next generation sequencing was performed for a panel of 131 known retinal dystrophy genes. Segregation analysis for all identified variants was completed.
The proband (II-1; 18-year-old) and a younger sibling (II-3; 13-year-old) had a phenotype consistent with early onset retinal dystrophy (EORD). Both had nystagmus and poor visual behaviour since infancy and ERGs performed at the age of five years showed non-detectable rod and cone function. BCVA at the most recent visit was 1.6 logMar or worse in both of them. Two other siblings [II-2 (17-year-old) and II-6 (6-month-old)] had an electrophysiological phenotype consistent with achromatopsia; fundus was normal in II-6 but demonstrated bilateral macular coloboma in II-2. Case II-2 had BCVA of 1.3 and 1.0 logMAR in the right and left eye, respectively. The proband’s mother (I-2) presented with a clinical phenotype consistent with mild autosomal recessive retinitis pigmentosa; at 45-years of age she still has moderate preservation of both rod and cone function. Cases I-1, II-4 and II-5 (53, 6 and 5 year-old, respectively) had normal eye exams; case II-4 has non-syndromic hearing loss. Molecular analysis revealed 2 homozygous, likely pathogenic variants in RD3 and CNGB3. Segregation analysis was performed.
Consanguinity is known to increase the risk of autosomal recessive inherited genetic disorders. This is a rare instance wherein at least three different inherited retinal dystrophies phenotypes are identified within the same pedigree.
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