Hypomorphic mutations in TRNT1 cause retinitis pigmentosa with erythrocytic microcytosis.

Retinitis pigmentosa (RP) is a highly heterogeneous group of disorders characterized by degeneration of the retinal photoreceptor cells and progressive loss of vision. While hundreds of mutations in more than 100 genes have been reported to cause RP, discovering the causative mutations in many patients remains a significant challenge. Exome sequencing in an individual affected with non-syndromic RP revealed two plausibly disease-causing variants in TRNT1, a gene encoding a nucleotidyltransferase critical for tRNA processing. A total of 727 additional unrelated individuals with molecularly uncharacterized RP were completely screened for TRNT1 coding sequence variants, and a second family was identified with two members who exhibited a phenotype that was remarkably similar to the index patient. Inactivating mutations in TRNT1 have been previously shown to cause a severe congenital syndrome of sideroblastic anemia, B-cell immunodeficiency, recurrent fevers and developmental delay (SIFD). Complete blood counts of all three of our patients revealed red blood cell microcytosis and anisocytosis with only mild anemia. Characterization of TRNT1 in patient-derived cell lines revealed reduced but detectable TRNT1 protein, consistent with partial function. Suppression of trnt1 expression in zebrafish recapitulated several features of the human SIFD syndrome, including anemia and sensory organ defects. When levels of trnt1 were titrated, visual dysfunction was found in the absence of other phenotypes. The visual defects in the trnt1-knockdown zebrafish were ameliorated by the addition of exogenous human TRNT1 RNA. Our findings indicate that hypomorphic TRNT1 mutations can cause a recessive disease that is almost entirely limited to the retina.

Extended Wear Bandage Contact Lenses Decrease Pain and Preserve Vision in Patients with Epidermolysis Bullosa: Case Series and Review of Literature.

Purpose: To demonstrate the therapeutic benefit of extended wear bandage contact lens (BCL) use in patients with epidermolysis bullosa (EB) suffering from recurrent, painful, and slow-to-heal corneal epithelial defects.Methods: Case reports of three patients.Results: We report ophthalmic treatment of three pediatric patients, two with recessive dystrophic EB (RDEB) and one with junctional EB (JEB), who suffered frequently recurrent corneal abrasions and were treated with 30-day extended-wear bandage contact lenses (BCLs), replaced every month for at least 1 year. Pain and frequency of corneal abrasions improved immediately, and the BCLs were well tolerated. Vision was maintained or improved in all cases. Corneal ulcers did not occur while on antibiotic prophylaxis.Conclusions: Continuous and prolonged BCL therapy in patients with EB can be an effective way to immediately alleviate pain, prevent recurrent abrasions, and improve patient quality of life.

Bilateral Squamosal Suture Craniosynostosis Presenting with Abducens Nerve Palsy and Severe Papilledema.

BACKGROUND: Patients with single-suture or minor suture craniosynostosis are typically asymptomatic at early presentation; intervention is aimed at reducing the risk of elevated intracranial pressure and associated developmental sequelae. Patients may be symptomatic in cases of major multisuture syndromic synostoses or delayed diagnosis. Clinical presentation in this context may include headaches, papilledema, cognitive delay, or behavioral issues. Cranial nerve palsies are atypical symptoms of intracranial hypertension in this patient population. CASE DESCRIPTION: An 11-month-old, otherwise healthy girl presented with bilateral severe papilledema and left abducens nerve palsy owing to nonsyndromic near-complete bilateral squamosal suture synostosis with associated incomplete sagittal and right lambdoid synostoses. The patient underwent urgent open cranial expansion, with resolution of her papilledema and improvement in eye position and motility. CONCLUSIONS: Cranial nerve palsies may be presenting symptoms of intracranial hypertension in patients with craniosynostosis. Multidisciplinary evaluation and treatment is paramount for appropriate management.