Papers by Cristina Villanueva-Mendoza
Ophthalmic Genetics, 2022
BACKGROUND Hereditary transthyretin amyloidosis (ATTR) is a multisystemic disease with autosomal ... more BACKGROUND Hereditary transthyretin amyloidosis (ATTR) is a multisystemic disease with autosomal dominant inheritance, characterized by the deposition of amyloid-insoluble proteins. We describe a case of vitreous amyloidosis as the initial presentation of ATTRv amyloidosis resulting from the rare Ile107Met (p.Ile127Met) pathogenic variant. MATERIALS AND METHODS Ophthalmic examination, multimodal imaging, vitreous biopsy, and genetic testing were performed to confirm the diagnosis. RESULTS A 44-year-old woman presented with blurred vision and floaters in both eyes (OU) for 1 year. The vitreous showed numerous strand-like opacities that were predominant in the anterior vitreous of OU. After a systemic workup and excluding malignancy, vitreous amyloidosis was suspected. Pars plana vitrectomy (PPV) of the left eye (OS) was performed, and a vitreous sample was obtained for histopathology. Homogeneous eosinophilic granular and filamentous deposits that showed an orange-red color with Congo red special stain were observed in the vitreous material, confirming vitreous amyloidosis. A PPV for the right eye (OD) was performed, and her vision at discharge was 20/20 OU. Systemic evaluation discarded neurologic or other systemic manifestations; however, there was familiar involvement in three generations with neurologic symptomatology, confirming an autosomal dominant inheritance pattern. Molecular analysis of the TTR gene showed a likely pathogenic variant Ile107Met (p.Ile127Met). CONCLUSIONS The present report describes a patient with ATTRv amyloidosis with initial vitreous involvement and the pathogenic variant Ile107Met (p.Ile127Met). It is important to consider vitreous amyloidosis as part of the non-malignant, non-infectious uveitis masquerade syndromes.
Purpose: Paired box gene 6 (PAX6) heterozygous mutations are well known to cause congenital non-s... more Purpose: Paired box gene 6 (PAX6) heterozygous mutations are well known to cause congenital non-syndromic aniridia. These mutations produce primarily protein truncations and have been identified in approximately 40%–80 % of all aniridia cases worldwide. In Mexico, there is only one previous report describing three intragenic deletions in five cases. In this study, we further analyze PAX6 variants in a group of Mexican aniridia patients and describe associated ocular findings. Methods: We evaluated 30 nonrelated probands from two referral hospitals. Mutations were detected by single-strand conformation polymorphism (SSCP) and direct sequencing, and novel missense mutations and intronic changes were analyzed by in silico analysis. One intronic variation (IVS2+9G>A), which in silico analysis suggested had no pathological effects, was searched in 103 unaffected controls. Results: Almost all cases exhibited phenotypes that were at the severe end of the aniridia spectrum with associate...
Revista medica del Instituto Mexicano del Seguro Social, 2019
BACKGROUND Zika is a flavivirus that can be transmitted transplacentally. Eye abnormalities have ... more 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...
Revista Médica del Hospital General de México, 2009
Alstrom syndrome (AS) is a rare autosomal recessively inherited disorder which affects multiple o... more Alstrom syndrome (AS) is a rare autosomal recessively inherited disorder which affects multiple organs and systems, the main features are cone–rod retinal dystrophy leading to juvenile blindness, progressive sensorineural hearing loss and obesity. Associated endocrinologic features include hyperinsulinemia, early-onset type 2 diabetes and hypertriglyceridemia. Other characteristics such as dilated cardiomyopathy, hepatic and urinary dysfunctions are also commonly observed in patients with this syndrome. Here we report a family with two sibilings affected by Alstrom syndrome and we analyzed the clinic phenotype and compare them with the literature.
Revista Mexicana de Oftalmología, 2006
La trisomía 21 es un síndrome de características fenotípicas determinadas. El primero en describi... more La trisomía 21 es un síndrome de características fenotípicas determinadas. El primero en describir el cuadro clínico y categorizar a los pacientes fue Langdon Down en 1866. Waardenburg, en 1932, propuso que este síndrome era causa de una anormalidad genética y en 1959 Lejeune, Gauthien y Turpis demostraron que la causa del síndrome era la trisomía del cromosoma 21. Los primeros en describir las anormalidades oftalmológicas que presentan estos pacientes fueron Séller y Osler en 1951 (1). Este síndrome se caracteriza por retraso mental, talla baja, hipotonía, braquicefalia, nariz peCatarata en pacientes con trisomía 21
Investigative Ophthalmology & Visual Science, 2013
Revista Mexicana de Oftalmología, 2010
Objetivos: Determinar cuales son las patologías oculares más comunes causantes de nistagmo congén... more Objetivos: Determinar cuales son las patologías oculares más comunes causantes de nistagmo congénito o infantil, así como la frecuencia de nistagmo congénito sensorial y motor. Material y métodos: Se revisaron los expedientes de pacientes pediátricos diagnosticados con nistagmo congénito o infantil en el servicio de Estrabismo de la Asociación para Evitar la Ceguera en México. De acuerdo con los datos del expediente se estableció el diagnóstico de la patología causante del nistagmo. En los casos sin diagnóstico definitivo se realizó valoración oftalmológica de genética y estudios complementarios. Resultados: Se estudiaron 63 pacientes con un rango de edad de 3 meses hasta 12 años. Se encontraron 34 pacientes con alteraciones oculares, diagnosticándose como nistagmo sensorial; 10 pacientes sin defectos oculares que fueron clasificados como nistagmo motor congénito y 3 pacientes como nistagmo neurológico. En 12 casos no se pudo establecer un diagnostico definitivo y se eliminaron 4 fi...
Revista Mexicana de Oftalmología, 2013
La homocistinuria es un error innato del metabolismo causado por la deficiencia de la cistationin... more La homocistinuria es un error innato del metabolismo causado por la deficiencia de la cistationina b-sintetasa, con herencia autosomica recesiva. El cuadro clinico se caracteriza por deficit mental, subluxacion del cristalino, cambios esqueleticos y tendencia a fenomenos tromboembolicos. Se reporta el caso de una paciente de 8 anos de edad con deficit mental, habito marfanoide, miopia alta y subluxacion del cristalino bilateral nasal inferior. Se realizo ecocardiograma el cual se encontro normal, la determinacion de homocisteina en plasma se encontro elevada: 309 μmol/L (5-16 μmol/L), con este ultimo dato se confirma el diagnostico de homocistinuria. ◗ Abstract
Introduction. Allgrove syndrome, also known as Triple A syndrome, is an autosomal recessive disor... more Introduction. Allgrove syndrome, also known as Triple A syndrome, is an autosomal recessive disorder characterized by adrenocorticotropin hormone (ACTH)-resistant adrenal insufficiency, achalasia and alacrima. Allgrove described siblings with isolated glucocorticoid failure, achalasia and defective tear production. It has also been associated with some neurologic abnormalities and there is a variable clinical presentation. The Triple A gene was identified by Tullio-Pullet et al and it is responsible for the production of a protein called ALADIN. Case report. We report a 7 years old patient with alacrima, optic atrophy and achalasia. Until now he has not had adrenal insufficiency. Conclusion. This entity is rare, some of the symptoms appear later in the development of the disease, including neurologic abnormalities and adrenal insufficiency. The ophtalmologist and the pediatrician must consider it in patients with alacrima or acalasia.
Investigative Ophthalmology & Visual Science, 2011
Genes, 2021
In this work, we aimed to provide the genetic diagnosis of a large cohort of patients affected wi... more 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%)...
Investigative Ophthalmology & Visual Science, 2013
Human Genetics, 2021
Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is... more Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf–blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15%) probands displayed other genetic entities with dual sensory impairment, including Alström syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (...
Ophthalmic Genetics, 2020
ABSTRACT Background Choroideremia is an X-linked chorioretinal dystrophy caused by mutations in t... more ABSTRACT Background Choroideremia is an X-linked chorioretinal dystrophy caused by mutations in the CHM gene. The main differential diagnosis is X-linked retinitis pigmentosa. Clinically, male patients that are affected by these two diseases have similar symptoms. This work aims to report a familial case of choroideremia initially diagnosed as X-linked retinitis pigmentosa with a novel mutation in the CHM gene, and the relevance of fundus autofluorescence (FAF) in female carriers. Materials and Methods A complete ophthalmological evaluation was done in a 37-year-old woman and her 53-year-old maternal uncle; the uncle had been diagnosed previously with X-linked retinitis pigmentosa. A visual field test, FAF imaging, full-field electroretinography, and a genetic test were performed. Results In the proband, the fundoscopy revealed diffuse changes in the retinal pigment epithelium in both eyes, and the FAF showed a speckled pattern of low- and high-density. The maternal uncle’s ophthalmological evaluation showed choroidal and retinal atrophy consistent with choroideremia. The molecular analysis revealed a pathogenic variant in the CHM gene, c.190–1 G > T. Conclusions In female carriers of choroideremia and X-linked retinitis pigmentosa, differential diagnosis may be challenging. A speckled pattern of low- and high-density in autofluorescence is commonly found in female carriers of choroideremia. FAF is a powerful tool for making a correct clinical diagnosis because the pattern in FAF is much more apparent than the visible retinal changes obtained by fundoscopy. Although it is crucial to perform molecular analysis to confirm the diagnosis, FAF is useful when genetic testing may not be readily available.
Ophthalmic Genetics, 2020
ABSTRACT Background Cat eye syndrome (CES) is a rare chromosomal disorder with a known incidence ... more ABSTRACT Background Cat eye syndrome (CES) is a rare chromosomal disorder with a known incidence of 1 per 50,000–150,000 live newborns. The classic triad of iris coloboma, anorectal malformations, and auricular abnormalities is present in 40% of patients. In addition, other ocular malformations and systemic defects can be present. The aim of this report is to present a patient with unilateral iris coloboma related to a mosaicism of cat eye syndrome. Methods A complete ophthalmological and systemic evaluation was performed in a three-year-old male. He also underwent a standard karyotype and FISH analysis with a probe against the 22q11.2 locus. Results The ophthalmological and systemic evaluation revealed a unilateral iris coloboma and ipsilateral auricular malformations. Karyotype analysis of blood leukocytes indicated the presence of a marker chromosome in 6% of the analyzed cells. FISH analysis showed three positive signals in 5.5% of the analyzed nucleus. Conclusion This patient presented two of the three classic manifestations of CES; interestingly, they were unilateral. The 22q11 duplication was identified by standard karyotype and confirmed with FISH. The present case demonstrates the importance of conducting a multidisciplinary approach in patients with congenital malformations associated with known syndromes.
Molecular Genetics & Genomic Medicine, 2020
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Genes, 2020
Aims: We aimed to validate the pathogenicity of genetic variants identified in inherited retinal ... more Aims: We aimed to validate the pathogenicity of genetic variants identified in inherited retinal dystrophy (IRD) patients, which were located in non-canonical splice sites (NCSS). Methods: After next generation sequencing (NGS) analysis (target gene panels or whole exome sequencing (WES)), NCSS variants were prioritized according to in silico predictions. In vivo and in vitro functional tests were used to validate their pathogenicity. Results: Four novel NCSS variants have been identified. They are located in intron 33 and 34 of ABCA4 (c.4774-9G>A and c.4849-8C>G, respectively), intron 2 of POC1B (c.101-3T>G) and intron 3 of RP2 (c.884-14G>A). Functional analysis detected different aberrant splicing events, including intron retention, exon skipping and intronic nucleotide addition, whose molecular effect was either the disruption or the elongation of the open reading frame of the corresponding gene. Conclusions: Our data increase the genetic diagnostic yield of IRD patie...
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Papers by Cristina Villanueva-Mendoza