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Tamar Ben-Yosef, Nitza Goldenberg-Cohen, Eyal Banin, Ben Cohen, Yael Zalzstein, Leah Rizel, Lina Basel-Vanagaite; Exome sequencing identifies mutations of both MYO7A and PDE6B in three siblings with retinitis pigmentosa. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3346. doi: https://doi.org/.
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Retinitis pigmentosa (RP), the most genetically heterogeneous disorder in humans, actually represents a group of pigmentary retinopathies characterized by night blindness followed by visual-field loss. RP can appear as either syndromic or nonsyndromic. One of the most common forms of syndromic RP is Usher syndrome, characterized by the combination of RP and hearing loss. The current work aimed to identify the underlying cause for the appearance of both syndromic and nonsyndromic RP in three siblings from a consanguineous Israeli Muslim Arab family.
Patients underwent a detailed ophthalmic examination, including funduscopy, electroretinography (ERG), optical coherence tomography (OCT), visual field and color vision testing. Affected individuals were studied by whole-genome homozygosity mapping followed by whole exome sequencing.
The family was found to segregate novel mutations of two different genes: MYO7A, causing type 1 Usher syndrome, and PDE6B, causing nonsyndromic RP. One affected child was homozygous for both mutations. Since the retinal phenotype seen in this patient results from overlapping pathologies, one might expect to find a very severe retinal degeneration. Indeed, he was diagnosed with RP based on an abnormal ERG at a very young age (9 months). However, this early diagnosis may be biased, as two of his older siblings have already been diagnosed, leading to increased awareness. At the age of 32 months he had relatively good vision with normal visual fields.
Here we present a rare case of three siblings with the same retinal phenotype (RP) and three different genotypes (MYO7A deficiency, PDE6B deficiency or both). This report further exhibits the genetic heterogeneity of RP, and demonstrates how consanguinity could increase intrafamilial clustering of multiple hereditary diseases. Moreover, it provides a unique opportunity to study the clinical implications of co-existence of null mutations in two RP-causative genes in a human patient.
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