Asunto(s)
Enfermedades Autoinmunes , Liquen Escleroso y Atrófico , Humanos , Estudios Retrospectivos , Femenino , Enfermedades Autoinmunes/epidemiología , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/inmunología , Liquen Escleroso y Atrófico/epidemiología , Liquen Escleroso y Atrófico/complicaciones , Liquen Escleroso y Atrófico/inmunología , Masculino , Persona de Mediana Edad , Adulto , AncianoAsunto(s)
Vitíligo , Liquen Escleroso Vulvar , Humanos , Vitíligo/diagnóstico , Liquen Escleroso Vulvar/diagnóstico , Liquen Escleroso Vulvar/patología , Liquen Escleroso Vulvar/complicaciones , Femenino , Diagnóstico Diferencial , Liquen Escleroso y Atrófico/diagnóstico , Liquen Escleroso y Atrófico/patologíaAsunto(s)
Herpes Zóster , Femenino , Humanos , Herpes Zóster/diagnóstico , Herpesvirus Humano 3 , VulvaAsunto(s)
Hipopigmentación , Liquen Escleroso y Atrófico , Vitíligo , Enfermedades de la Vulva , Liquen Escleroso Vulvar , Neoplasias de la Vulva , Femenino , Humanos , Liquen Escleroso Vulvar/complicaciones , Liquen Escleroso Vulvar/diagnóstico , Vitíligo/diagnóstico , Liquen Escleroso y Atrófico/complicaciones , Liquen Escleroso y Atrófico/diagnóstico , VulvaRESUMEN
PURPOSE: To provide the initial confirmation of the c.1772C>T (p.Ser591Phe) mutation in the transforming growth factor-ß-induced (TGFBI) gene as being associated with variant lattice corneal dystrophy (LCD). METHODS: Ophthalmologic examination of the proband was performed with slit lamp biomicroscopy. Saliva was collected as a source of DNA for screening all 17 exons of TGFBI, after which three family members were selectively screened for variants in exon 13. Rosetta-based structure prediction was used to calculate changes in TGFBI protein (TGFBIp) stability secondary to the c.1772C>T (p.Ser591Phe) missense mutation. RESULTS: Slit lamp examination of the 38-year-old proband revealed a clear cornea right eye and unilateral, discrete, and branching lattice lines in the anterior and mid-stroma of the central cornea left eye. Screening of TGFBI in the proband revealed a heterozygous missense mutation in exon 13 (c.1772C>T (p.Ser591Phe)) that was also identified in her affected mother but not in her brother or maternal grandmother. Calculated energy change in Rosetta (ΔΔG) for the TGFBIp variant p.Ser591Phe was 23.5, indicating a thermodynamic destabilization resulting from energetic frustration. CONCLUSIONS: The p.Ser591Phe mutation in TGFBI is associated with an unilateral variant of LCD. Rosetta-predicted stability changes indicate that the p.Ser591Phe variant is destabilizing, which is consistent with other observations for LCD-causing mutations.
Asunto(s)
Neuropatías Amiloides Familiares , Distrofias Hereditarias de la Córnea , Proteínas de la Matriz Extracelular , Factores de Crecimiento Transformadores , Adulto , Distrofias Hereditarias de la Córnea/diagnóstico , Distrofias Hereditarias de la Córnea/genética , Análisis Mutacional de ADN , Proteínas de la Matriz Extracelular/genética , Femenino , Humanos , Masculino , Mutación , Mutación Missense , Linaje , Factor de Crecimiento Transformador beta , Factores de Crecimiento Transformadores/genéticaRESUMEN
Meesmann epithelial corneal dystrophy (MECD) is a rare dominantly inherited disorder that is characterized by corneal epithelial microcysts and is associated with mutations in the keratin 3 (KRT3) and keratin 12 (KRT12) genes. In this study, we report a novel mutation in the KRT12 gene in a Vietnamese pedigree with MECD. Slit-lamp examination was performed on each of the 7 recruited members of a Vietnamese family to identify characteristic features of MECD. After informed consent was obtained from each individual, genomic DNA was isolated from saliva samples and screening of KRT3and KRT12 genes was performed by Sanger sequencing. The proband, a 31-year-old man, complained of a 1-year history of eye irritation and photophobia. Slit-lamp examination revealed intraepithelial microcysts involving only the corneal periphery in each eye with clear central corneas and no stromal or endothelial involvement. Three family members demonstrated similar intraepithelial microcysts, but with diffuse involvement, extended from limbus to limbus. Sanger sequencing of KRT3 (exon 7) and KRT12 (exons 1 and 6) in the proband revealed a novel heterozygous KRT12 variant (c.1273G>A [p.Glu425Lys]) that was present in the three affected family members but was absent in the three family members with clear corneas. This study is the first report of a Vietnamese family affected with MECD, associated with an atypical peripheral corneal epithelial phenotype in the proband and a novel mutation in KRT12.