RESUMEN
PURPOSE: To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache. METHODS: Independent discovery exome and genome sequencing in families 1, 2, and 3, and confirmation in families 4 and 5. Expression of wild-type messenger RNA and protein in human and mouse tissues and cell lines. Ciliary assays in fibroblasts from affected and unaffected family members. RESULTS: We found the heterozygous missense variant in the É-kinase gene, ALPK1, (c.710C>T, [p.Thr237Met]), segregated with disease in all five families. All patients shared the ROSAH phenotype with additional low-grade ocular inflammation, pancytopenia, recurrent infections, and mild renal impairment in some. ALPK1 was notably expressed in retina, retinal pigment epithelium, and optic nerve, with immunofluorescence indicating localization to the basal body of the connecting cilium of the photoreceptors, and presence in the sweat glands. Immunocytofluorescence revealed expression at the centrioles and spindle poles during metaphase, and at the base of the primary cilium. Affected family member fibroblasts demonstrated defective ciliogenesis. CONCLUSION: Heterozygosity for ALPK1, p.Thr237Met leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder.
Asunto(s)
Nervio Óptico/patología , Proteínas Quinasas/genética , Retina/metabolismo , Distrofias Retinianas/genética , Exoma/genética , Femenino , Heterocigoto , Humanos , Hipohidrosis/genética , Hipohidrosis/patología , Masculino , Trastornos Migrañosos/genética , Trastornos Migrañosos/patología , Mutación Missense/genética , Nervio Óptico/metabolismo , Linaje , Fenotipo , Retina/patología , Distrofias Retinianas/patología , Esplenomegalia/genética , Esplenomegalia/patologíaRESUMEN
PURPOSE: To report the persistence of choroidal lesions despite fluocinolone acetonide intravitreal implants and their resolution with oral prednisone treatment. METHODS: Retrospective chart review of a birdshot chorioretinopathy patient at a tertiary referral clinic. RESULTS: Indocyanine angiography revealed resolution of choroidal lesions with oral prednisone and recurrence after discontinuation of oral prednisone. CONCLUSION: Choroidal lesions responded to oral prednisone despite bilateral active fluocinolone acetonide intravitreal implant in a birdshot chorioretinopathy patient.
Asunto(s)
Retinocoroidopatía en Perdigonada , Fluocinolona Acetonida , Retinocoroidopatía en Perdigonada/tratamiento farmacológico , Implantes de Medicamentos , Fluocinolona Acetonida/uso terapéutico , Humanos , Estudios Retrospectivos , Insuficiencia del TratamientoRESUMEN
Autoimmune retinopathy (AIR) is a rare immune-mediated retinopathy associated with circulating antiretinal antibodies (ARAs). Other prominent features of AIR include visual field deficits and photoreceptor dysfunction in the setting of progressive unexplained vision loss. The role of inflammation is poorly understood in AIR. Since cytokines play a central role in the initiation and development of inflammation, we evaluated the presence of proinflammatory cytokines and chemokines in AIR patient sera. We demonstrate that IL-6 and CXCL9 are both elevated in AIR patient sera. Moreover, the presence and concentration of these 2 molecules appear to correlate with AIR patient disease severity. This cytokine profile, IL-6 and CXCL9, has been described to participate in a variety of autoimmune and inflammatory diseases. Our study provides support for an activated inflammatory process in AIR and identifies possible mechanisms that can drive autoimmunity in this disease.