BackgroundVariable expressivity is a well-known phenomenon in which patients with mutations in one gene display varying degrees of clinical severity, potentially displaying only subsets of the clinical manifestations associated with the multisystem disorder linked to the gene. This remains an incompletely understood phenomenon with proposed mechanisms ranging from allele-specific to stochastic.ResultsWe report three consanguineous families in which an isolated ocular phenotype is linked to a novel 3′ UTR mutation in SLC4A4, a gene known to be mutated in a syndromic form of intellectual disability with renal and ocular involvement. Although SLC4A4 is normally devoid of AU-rich elements (AREs), a 3′ UTR motif that mediates post-transcriptional control of a subset of genes, the mutation we describe creates a functional ARE. We observe a marked reduction in the transcript level of SLC4A4 in patient cells. Experimental confirmation of the ARE-creating mutation is shown using a post-transcriptional reporter system that reveals consistent reduction in the mRNA-half life and reporter activity. Moreover, the neo-ARE binds and responds to the zinc finger protein ZFP36/TTP, an ARE-mRNA decay-promoting protein.ConclusionsThis novel mutational mechanism for a Mendelian disease expands the potential mechanisms that underlie variable phenotypic expressivity in humans to also include 3′ UTR mutations with tissue-specific pathology.
Post-keratoplasty endophthalmitis was associated with poor visual and structural outcome. Gram-positive organisms were the most common cause of infection. Early vitrectomy may reduce functional and structural damage associated with endophthalmitis.
AIM: To evaluate the causes of phakic implantable collamer lens (ICL) exchange/explantation in patients with and without keratoconus (KC) at two tertiary hospitals in Riyadh, Saudi Arabia.
METHODS: A retrospective chart review of all patients who underwent ICL (model V4c with central port) exchange/explantation was performed using the electronic medical record systems. All available preoperative and postoperative data were documented for each patient.
RESULTS: Over 7y, 2283 ICL implantation procedures were performed; 46 implants (2%) required exchange (21 implants)/explantation (25 implants), of which 14 cases (30.4%) were patients with KC. Indications for ICL exchange/explantation in non-KC group were vault measurement, cataract formation, increased intraocular pressure, inaccurate refraction, and patient dissatisfaction in 22 (68.75%), 4 (12.5%), 3 (9.37%), 2 (6.25%), and 1 (3.12%) case, respectively. The most common indication for ICL exchange/explantation in the KC group was inaccurate vault sizing in 11 patients (78.57%), inaccurate refraction in 2 patients (14.28%), and patient dissatisfaction postoperatively in 1 (7.14%) case.
CONCLUSION: ICL implantation results in predictable refractive outcomes over the long term with exchange/explantation rates comparable to previous literature. Improper vault size is the most common cause of ICL exchange/explantation among patients with or without KC.
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