RESUMO
PURPOSE: Human ophthalmomyiasis is a rare ocular parasitosis that results from the accidental infestation of dipteran larvae of several species, including Oestrus ovis (Linnaeus, 1758). This study aims to present the fourth documented human case of ophthalmomyiasis in Mexico, identifying the etiological agent through morphological and molecular analyses. Additionally, we investigated the phylogenetic position and genetic distances among different specimens globally characterized based on mitochondrial Cox1 sequences. METHODS: A total of five larval specimens were extracted from the patient's eye, with two specimens allocated for identification based on morphological features using a stereomicroscope, and the remaining three preserved in absolute ethanol, one of them used for subsequent analysis using molecular methods. The mitochondrial Cox1 region was amplified and sequenced using automated Sanger sequencing. The resulting sequence was deposited in GenBank under accession number OR440699 and subjected to BlastN analysis against 35 other Cox1 sequences of O. ovis from GenBank. The identity and phylogenetic position of the strains were further explored using parsimony and maximum likelihood phylogenetic methods. RESULTS: Morphological examination of the larval specimens extracted from the patient's eye unequivocally identified them as O. ovis species. BlastN analysis and comprehensive phylogenetic investigations involving a total of 36 Cox1 sequences confirmed the taxonomic identity of the larvae. Notably, our sequence was positioned within the cluster formed by the Brazilian and two Iranian samples. This finding underscores a shared genetic ancestry among these distinct geographical isolates and provides valuable insights into the evolutionary relationships within O. ovis populations. CONCLUSION: The presence of O. ovis infestation in Mexico City suggests potential shifts in environmental conditions favoring fly proliferation, highlighting the need for vigilance in urban healthcare settings.
Assuntos
Dípteros , Infecções Oculares Parasitárias , Larva , Miíase , Filogenia , Animais , Miíase/parasitologia , Miíase/veterinária , Larva/genética , Larva/classificação , México , Humanos , Dípteros/genética , Dípteros/classificação , Dípteros/parasitologia , Infecções Oculares Parasitárias/parasitologia , Infecções Oculares Parasitárias/veterinária , Infecções Oculares Parasitárias/diagnóstico , Masculino , FemininoRESUMO
Primary congenital glaucoma (PCG) is one of the leading causes of visual damage and blindness, severely affecting the quality of life of affected children. It is characterized by cupping of the optic disc and loss of ganglion cells due to elevated intraocular pressure. While most PCG patients exhibit epiphora, photophobia, and buphthalmos with corneal opacity, variability in phenotypic manifestations is not uncommon. Prompt diagnosis and treatment of PCG affected individuals becomes relevant to preserve visual function throughout their lives. Most PCG cases are sporadic or autosomal recessive; however, an incompletely dominant autosomal dominant form arising from mutations in the TEK gene has recently been demonstrated. Here, we describe the clinical and mutational features of a cohort of Mexican patients with TEK-related PCG. Our results support the involvement of the TEK gene as an important cause of the disease in our ethnic group and expand the mutational spectrum causing PCG by reporting 10 novel disease-causing variants.
Assuntos
Glaucoma , Mutação , Linhagem , Fenótipo , Humanos , Feminino , Mutação/genética , Masculino , México/epidemiologia , Glaucoma/genética , Glaucoma/patologia , Glaucoma/congênito , Criança , Pré-Escolar , Lactente , Predisposição Genética para Doença , Estudos de Associação Genética , Análise Mutacional de DNA , Estudos de CoortesRESUMO
Inherited and developmental eye diseases are quite diverse and numerous, and determining their genetic cause is challenging due to their high allelic and locus heterogeneity. New molecular approaches, such as whole exome sequencing (WES), have proven to be powerful molecular tools for addressing these cases. The present study used WES to identify the genetic etiology in ten unrelated Mexican pediatric patients with complex ocular anomalies and other systemic alterations of unknown etiology. The WES approach allowed us to identify five clinically relevant variants in the GZF1, NFIX, TRRAP, FGFR2 and PAX2 genes associated with Larsen, Malan, developmental delay with or without dysmorphic facies and autism, LADD1 and papillorenal syndromes. Mutations located in GZF1 and NFIX were classified as pathogenic, those in TRRAP and FGFR2 were classified as likely pathogenic variants, and those in PAX2 were classified as variants of unknown significance. Protein modeling of the two missense FGFR2 p.(Arg210Gln) and PAX2 p.(Met3Thr) variants showed that these changes could induce potential structural alterations in important functional regions of the proteins. Notably, four out of the five variants were not previously reported, except for the TRRAP gene. Consequently, WES enabled the identification of the genetic cause in 40% of the cases reported. All the syndromes reported herein are very rare, with phenotypes that may overlap with other genetic entities.
Assuntos
Sequenciamento do Exoma , Anormalidades do Olho , Fator de Transcrição PAX2 , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos , Humanos , Masculino , Feminino , Criança , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Fator de Transcrição PAX2/genética , Pré-Escolar , Anormalidades do Olho/genética , Lactente , Mutação , Adolescente , Predisposição Genética para DoençaRESUMO
In this work, we aimed to provide the genetic diagnosis of a large cohort of patients affected with inherited retinal dystrophies (IRDs) from Mexico. Our data add valuable information to the genetic portrait in rare ocular diseases of Mesoamerican populations, which are mostly under-represented in genetic studies. A cohort of 144 unrelated probands with a clinical diagnosis of IRD were analyzed by next-generation sequencing using target gene panels (overall including 346 genes and 65 intronic sequences). Four unsolved cases were analyzed by whole-exome sequencing (WES). The pathogenicity of new variants was assessed by in silico prediction algorithms and classified following the American College of Medical Genetics and Genomics (ACMG) guidelines. Pathogenic or likely pathogenic variants were identified in 105 probands, with a final diagnostic yield of 72.9%; 17 cases (11.8%) were partially solved. Eighteen patients were clinically reclassified after a genetic diagnostic test (17.1%). In our Mexican cohort, mutations in 48 genes were found, with ABCA4, CRB1, RPGR and USH2A as the major contributors. Notably, over 50 new putatively pathogenic variants were identified. Our data highlight cases with relevant clinical and genetic features due to mutations in the RAB28 and CWC27 genes, enrich the novel mutation repertoire and expand the IRD landscape of the Mexican population.
Assuntos
Heterogeneidade Genética , Fenótipo , Doenças Retinianas/genética , Adulto , Feminino , Humanos , Masculino , México , Mutação , Doenças Retinianas/patologiaRESUMO
PURPOSE: Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant disorder that affects the anterior segment of the eye. The aim of this study was to examine the PITX2 gene to identify possible novel mutations in Pakistani and Mexican families affected by the ARS phenotype. METHODS: Three unrelated probands with a diagnosis of ARS were recruited for this study. Genomic DNA was isolated from the peripheral blood of the probands and their family members. Polymerase chain reaction and Sanger sequencing were used for the analysis of coding exons and the flanking intronic regions of the PITX2 gene. Bioinformatics tools and database (VarSome, Provean, and MutationTaster, SIFT, PolyPhen-2, and HOPE) were evaluated to explore missense variants. RESULTS: We identified novel heterozygous variations in the PITX2 gene that segregated with the ARS phenotype within the families. The variant NM_153426.2(PITX2):c.226G > T or p.(Ala76Ser) and the mutation NM_153426.2(PITX2):c.455G > A or p.(Cys152Tyr) were identified in two Pakistani pedigrees, and the mutation NM_153426.2(PITX2):c.242_265del or p.(Lys81_Gln88del), segregated in a Mexican family. CONCLUSION: Our study extends the spectrum of PITX2 mutations in individuals with ARS, enabling an improved diagnosis of this rare but serious syndrome.
Assuntos
Segmento Anterior do Olho/anormalidades , Anormalidades do Olho/genética , Oftalmopatias Hereditárias/genética , Proteínas de Homeodomínio/genética , Mutação , Fatores de Transcrição/genética , Adolescente , Segmento Anterior do Olho/patologia , Criança , Anormalidades do Olho/patologia , Oftalmopatias Hereditárias/patologia , Feminino , Heterozigoto , Humanos , Masculino , Linhagem , Proteína Homeobox PITX2RESUMO
BACKGROUND: Postzygotic KRAS, HRAS, NRAS, and FGFR1 mutations result in a group of mosaic RASopathies characterized by related developmental anomalies in eye, skin, heart, and brain. These oculocutaneous disorders include oculoectodermal syndrome (OES) encephalo-cranio-cutaneous lipomatosis (ECCL), and Schimmelpenning-Feuerstein-Mims syndrome (SFMS). Here, we report the results of the clinical and molecular characterization of a novel cohort of patients with oculocutaneous mosaic RASopathies. METHODS: Two OES, two ECCL, and two SFMS patients were ascertained in the study. In addition, two subjects with unilateral isolated epibulbar dermoids were also enrolled. Molecular analysis included PCR amplification and Sanger sequencing of KRAS, HRAS, NRAS, and FGFR1 genes in DNA obtained from biopsies (skin/epibulbar dermoids), buccal mucosa, and blood leukocytes. Massive parallel sequencing was employed in two cases with low-level mosaicism. RESULTS: In DNA from biopsies, mosaicism for pathogenic variants, including KRAS p.Ala146Thr in two OES subjects, FGFR1 p.Asn546Lys and KRAS p.Ala146Val in ECCL patients, and KRAS p.Gly12Asp in both SFMS patients, was demonstrated. No mutations were shown in DNA from conjunctival lesions in two subjects with isolated epibubar dermoids. CONCLUSION: Our study allowed the expansion of the clinical spectrum of mosaic RASopathies and supports that mosaicism for recurrent mutations in KRAS and FGFR1 is a commonly involved mechanism in these rare oculocutaneous anomalies.
Assuntos
Cisto Dermoide/genética , Displasia Ectodérmica/genética , Oftalmopatias/genética , Lipomatose/genética , Síndromes Neurocutâneas/genética , Nevo Sebáceo de Jadassohn/genética , Fenótipo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Cisto Dermoide/patologia , Displasia Ectodérmica/patologia , Oftalmopatias/patologia , GTP Fosfo-Hidrolases/genética , Humanos , Lipomatose/patologia , Proteínas de Membrana/genética , Mosaicismo , Síndromes Neurocutâneas/patologia , Nevo Sebáceo de Jadassohn/patologia , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
BACKGROUND: Zika is a flavivirus that can be transmitted transplacentally. Eye abnormalities have been reported in 70% of Zika cases, and 41.7% of them can occur in the absence of microcephaly. The most common ocular abnormalities are macular atrophy, optic atrophy and chorioretinal coloboma. The objective was to report the case of eye disorders associated with Zika, acquired transplacentally, despite negative results for TORCH, and serology and PCR analyses for Zika. CLINICAL CASE: 9-month-old female patient, born in Chiapas, Mexico, brought to an ophthalmologic evaluation because she did not follow objects. As family background patient's mother had Zika, confirmed serologically at 9 weeks gestation. Physical examination revealed microcephaly, redundant skin on neck, joint stiffness and delayed psychomotor development. Ophthalmological examination revealed in right eye atrophy of the optic nerve, and left eye with exotropia, macular scar and optic nerve aplasia. TORCH profile and serology and PCR for Zika were negative. CONCLUSIONS: Despite the negative serology for Zika, given the history of pregnancy and the pre and post-natal clinical manifestations, diagnosis of embryopathy secondary to Zika infection with optic nerve aplasia, chorioretinal atrophy, macular scar, microcephaly and global neurodevelopmental delay was made.
INTRODUCCIÓN: el Zika es un flavivirus que puede ser transmitido de forma transplacentaria. Las anomalías oculares han sido reportadas en un 70% de los casos y se ha visto que 41.7% de ellas pueden ocurrir en ausencia de microcefalia. Las alteraciones oculares más comunes son: atrofia macular, atrofia óptica y coloboma coriorretiniano. El objetivo de este estudio fue reportar un caso de alteraciones oculares asociadas a Zika, adquirido de forma transplacentaria, a pesar de los resultados negativos para el perfil TORCH y Zika de los análisis de serología y PCR. CASO CLÍNICO: paciente femenina de nueve meses de edad, originaria de Chiapas, México, traída a revisión oftalmológica porque no seguía objetos. Como antecedentes, la paciente tenía madre con diagnóstico de Zika confirmado serológicamente a las nueve semanas de gestación. A la exploración física se encontró microcefalia, piel redundante en cuello, rigidez articular y retraso en el desarrollo psicomotor. A la exploración oftalmológica fueron evidentes atrofia del nervio óptico de ojo derecho, ojo izquierdo con exotropía, cicatriz macular y aplasia del nervio óptico. Tanto el perfil TORCH como la serología y la PCR para Zika fueron negativos. CONCLUSIONES: a pesar de la serología negativa para Zika, dados los antecedentes de la gestación y las manifestaciones clínicas pre y postnatales se integró el diagnóstico de embriopatía secundaria a infección por Zika con aplasia del nervio óptico, atrofia coriorretiniana, cicatriz macular, microcefalia y retraso global del neurodesarrollo.
Assuntos
Microcefalia/diagnóstico , Infecção por Zika virus/congênito , Infecção por Zika virus/diagnóstico , Diagnóstico Tardio , Deficiências do Desenvolvimento/diagnóstico , Exotropia/diagnóstico , Feminino , Humanos , Lactente , Atrofia Óptica/diagnóstico , Nervo Óptico/anormalidades , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Primeiro Trimestre da Gravidez , Anormalidades da Pele/diagnóstico , Infecção por Zika virus/transmissãoRESUMO
PURPOSE: The aim of this study was to describe a case of severe keratitis-ichthyosis-deafness (KID) syndrome with ocular surface squamous neoplasia. METHODS: The affected patient underwent complete ocular and systemic examinations. The molecular studies included polymerase chain reaction amplification and automated DNA sequencing of the complete gap junction beta-2 (GJB2) gene coding sequence. RESULTS: A 30-year-old man presented with generalized erythro-hyperkeratosis and deafness and complaints of decreased visual acuity, tearing, and photophobia. Ophthalmic examination showed corneal erosion, vascularization, and a gray gelatinous lesion partially covering the right cornea, suggestive of squamous neoplasia. The clinical features were characteristic of KID syndrome. This diagnosis was confirmed with a DNA analysis showing the pathogenic variant p.D50N in the GJB2 gene. Presumed squamous neoplasia was treated with topical interferon α2b. CONCLUSIONS: KID syndrome is a very rare disease that has been reported with an incremental incidence of squamous cell carcinoma of the mucous membranes and skin (12%-15%). Here, we presented a case of severe systemic KID syndrome with ocular surface squamous neoplasia.
Assuntos
Carcinoma de Células Escamosas/patologia , Doenças da Córnea/patologia , Neoplasias Oculares/patologia , Ceratite/patologia , Adulto , Humanos , Masculino , FenótipoRESUMO
Tietz syndrome and Waardenburg syndrome type 2A are allelic conditions caused by MITF mutations. Tietz syndrome is inherited in an autosomal dominant pattern and is characterized by congenital deafness and generalized skin, hair, and eye hypopigmentation, while Waardenburg syndrome type 2A typically includes variable degrees of sensorineural hearing loss and patches of de-pigmented skin, hair, and irides. In this paper, we report two unrelated families with MITF mutations. The first family showed an autosomal dominant pattern and variable expressivity. The second patient was isolated. MITF gene analysis in the first family demonstrated a c.648A>C heterozygous mutation in exon 8 c.648A>C; p. (R216S), while in the isolated patient, an apparently de novo heterozygous c.1183_1184insG truncating mutation was demonstrated in exon 10. All patients except one had bilateral reduced ocular anteroposterior axial length and a high hyperopic refractive error corresponding to posterior microphthalmos, features that have not been described as part of the disease. Our results suggest that posterior microphthalmos might be part of the clinical characteristics of Tietz/Waardenburg syndrome type 2A and expand both the clinical and molecular spectrum of the disease. © 2016 Wiley Periodicals, Inc.