Immunohistochemical characterization of cytokeratins in the abnormal corneal endothelium of posterior polymorphous corneal dystrophy patients

Jirsová, Kateřina; Merjava, Stanislava; Martincova, Radka; Gwilliam, Rhian; Ebenezer, Neil D.; Lišková, Petra; Filipec, Martin

doi:10.1016/j.exer.2006.12.006

Cited by 53 publications

(41 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…30 Interestingly, the corneal endothelium from PPCD3 patients exhibits increased expression of markers for an epithelial cell phenotype, such as keratins 7 and 19. 2,3 Patients with PPCD also have multilayering of the corneal endothelium that is probably due to uncontrolled growth of a dividing endothelium. [2][3][4] The proportion of PPCD cases attributed to mutations in ZEB1 has been reported to be between 9 and 34%.…”

Section: Discussionmentioning

confidence: 99%

“…2,3 Patients with PPCD also have multilayering of the corneal endothelium that is probably due to uncontrolled growth of a dividing endothelium. [2][3][4] The proportion of PPCD cases attributed to mutations in ZEB1 has been reported to be between 9 and 34%. [9][10][11][12][14][15][16][17] Our results demonstrate that the number of cases with PPCD3 is underestimated, because standard screening techniques do not detect deletions spanning such large regions.…”

Section: Discussionmentioning

confidence: 99%

“…1 Endothelial cells from affected corneas demonstrate characteristics of epithelial cells including the ability to proliferate, leading to focal formation of multilayered areas, and multilamination of Descemet membrane. [2][3][4] PPCD is genetically heterogeneous with three identified loci; PPCD1 (OMIM #122000) on chromosome 20p with a currently undefined causative gene, [5][6][7] PPCD2 (OMIM #609140) associated with mutations in COL8A2, 8 and PPCD3 (OMIM #609141) caused by mutations in ZEB1. 9 To date, over 30 heterozygous nonsense and frameshifting mutations in ZEB1 have been identified.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Heterozygous deletions at the ZEB1 locus verify haploinsufficiency as the mechanism of disease for posterior polymorphous corneal dystrophy type 3

Lišková

Evans²,

Davidson³

et al. 2015

Eur J Hum Genet

Self Cite

View full text Add to dashboard Cite

A substantial proportion of patients with posterior polymorphous corneal dystrophy (PPCD) lack a molecular diagnosis. We evaluated 14 unrelated probands who had a clinical diagnosis of PPCD who were previously determined to be negative for mutations in ZEB1 by direct sequencing. A combination of techniques was used including whole-exome sequencing (WES), single-nucleotide polymorphism (SNP) array copy number variation (CNV) analysis, quantitative real-time PCR, and long-range PCR. Segregation of potentially pathogenic changes with disease was confirmed, where possible, in family members. A putative run of homozygosity on chromosome 10 was identified by WES in a three-generation PPCD family, suggestive of a heterozygous deletion. SNP array genotyping followed by long-range PCR and direct sequencing to define the breakpoints confirmed the presence of a large deletion that encompassed multiple genes, including ZEB1. Identification of a heterozygous deletion spanning ZEB1 prompted us to further investigate potential CNVs at this locus in the remaining probands, leading to detection of two additional heterozygous ZEB1 gene deletions. This study demonstrates that ZEB1 mutations account for a larger proportion of PPCD than previously estimated, and supports the hypothesis that haploinsufficiency of ZEB1 is the underlying molecular mechanism of disease for PPCD3.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Heterozygous deletions at the ZEB1 locus verify haploinsufficiency as the mechanism of disease for posterior polymorphous corneal dystrophy type 3

Lišková

Evans²,

Davidson³

et al. 2015

Eur J Hum Genet

Self Cite

View full text Add to dashboard Cite

show abstract

“…El complejo de citoqueratinas 8/18 es considerado un marcador específico de células de la luz de los conductos y de epitelios simples de humana, algo que puede diferir si lo comparamos con un estudio en ratones, debido principalmente a los anticuerpos que reconocen proteínas diferentes. El patrón de expresión de las citoqueratinas 8 y 18 puede ser actualmente monitorizado mediante ingeniería transgénica en ratones a partir de una proteína verde fluorescente bajo el control del promotor de una de dichas citoqueratinas 40 ; éste es un hecho fundamental para el avance en el estudio de estos filamentos 22 . La citoqueratina 7 fue positiva en todas las etapas de estudio.…”

Section: Figura 6 Expresión De La Citoqueratina 14 En Glándula Mamarunclassified

“…De hecho en la epidermis se sintetizan las citoqueratinas 1 y la 10, en la córnea la 3 y la 12 21 , en el esófago la 4 y la 13, en la epidermis palmo-plantar la 9, y la 6 en los brotes terminales. El endotelio corneal, formado por una capa única de células planas hexagonales, también expresa el complejo 8/18 22 . Las queratinas expresadas principalmente en epitelios simples son llamadas SEK's (Queratinas de Epitelios Simples) y aquí se engloban la 7, 8, 18, 19, 20, 23 y 24 23 .…”

Section: Introductionunclassified

El citoesqueleto celular en la glándula mamaria y su aplicación diagnóstica

Pérez¹,

Rodriguez²

2011

Sanid. Mil.

View full text Add to dashboard Cite

Sanid. mil. 2011; 67 (2): 92-97; ISSN: 1887-8571 RESUMEN Objetivos: Valorar la importancia de las modificaciones que aparecen en el citoesqueleto celular (en particular a nivel de unos filamentos intermedios denominados queratinas) a lo largo de los cambios que sufre la glándula mamaria, con especial referencia a la lactación. Su expresión será diferente y servirá como método de contraste. Diseño: 40 ratones distribuidos en cinco grupos según la etapa de estudio. El esquema experimental es común para todos ellos. Material y métodos: Análisis inmunohistoquímico de las muestras procedentes de las glándulas mamarias para evidenciar modificaciones a nivel de las citoqueratinas y comparación con otros estudios en diferentes modelos animales. Resultados: Cada citoqueratina presenta una expresión diferente según sea la estirpe celular y el periodo de lactación. Se diferencian mediante el uso de anticuerpos específicos marcados. Conclusiones: La expresión citoqueratínica varía de manera fisiológica y en células tumorales. La detección inmunohistoquímica de citoqueratinas puede servir como método de diagnóstico complementario.PALABRAS CLAVE: Citoesqueleto, filamentos intermedios, citoqueratina, mama, cáncer.The cellular cytoskeleton in the mammary gland and its diagnostic application SUMMARY: Objectives: To assess the importance of the changes that appear into the cytoskeleton (especially referred to some specific intermediate filaments called keratins) through different stages the mammary gland bears, focusing on the lactation. Their expression will be different in pathological conditions and this will be useful for contrasting other procedures. Design: 40 mice distributed into five groups according to the stage of study. The experimental project is the same for everyone. Material and methods: Immunohistochemical analysis from samples obtained from mammary glands in order to show changes into cytokeratin expression and comparison with other researches in different animal models. Results: The expression of every cytokeratin is different according to the cell lineage and the lactation period. Specific antibodies can reveal it. Conclusions: The cytokeratinic pattern changes in a physiological sense and also in malignant processes. Immunohistochemical detection of cytokeratins may be useful as complementary diagnosis.KEYWORDS: Cytoskeleton, intermediate filaments, cytokeratin, mammary gland, cancer. INTRODUCCIÓNEl cáncer de mama es el más frecuente en la población femenina española con una tasa de incidencia de 40-75 casos por cada 100.000 mujeres. Es la primera causa de muerte por tumores en mujeres en España y la segunda en EEUU tras el cáncer de pulmón 1 . El 75% de los casos aparece en mujeres de más de cincuenta años. Es el responsable de casi el 30% de fallecimientos por causa de cáncer, aunque esta cifra tiende a disminuir gracias a su detección precoz y a los nuevos tratamientos. En el caso de varones supone menos del 1% de todos los casos de cáncer de mama, con un 0,1% de mortalidad 2 .Estudios recientes sugier...

show abstract

Further Genetic and Clinical Insights of Posterior Polymorphous Corneal Dystrophy 3

et al. 2013

Self Cite

View full text Add to dashboard Cite

Posterior polymorphous corneal dystrophy (PPCD) is a very rare disorder characterized by primary changes of the posterior corneal layers. Sequence variants in 3 genes are associated with the development of PPCD, including ZEB1 that is responsible for PPCD3. Evidence suggests at least 1 more gene remains to be identified. OBJECTIVE To determine the molecular genetic cause of PPCD3. DESIGN We performed extensive ophthalmological examination, including rotating Scheimpflug imaging technology and specular microscopy, and direct sequencing of the ZEB1 coding region. Comprehensive review of published PPCD3-causing variants was undertaken. SETTING Ophthalmology department of a university hospital. PARTICIPANTS Four Czech probands. MAIN OUTCOMES AND MEASURES Results of ophthalmological examination and direct sequencing of the ZEB1 coding region. RESULTS The following 2 novel frameshift mutations within ZEB1 were identified: c.2617dup in exon 8 in a 22-year-old woman, considered to be most likely de novo in origin, and c.698dup in exon 6 in a 20-year-old man. The first patient had mild changes consistent with PPCD and bilateral best-corrected visual acuity of 1.00. The corneal phenotype of the patient in the second case was more severe, with best-corrected visual acuity of 0.40 OD and 0.05 OS. Corneas of both probands were abnormally steep (keratometry readings, flat Ն 47.4 diopters [D] and steep Ն 49.2 D) with increased pachymetry values but no pattern indicative of keratoconus. Specular microscopy in both patients revealed reduced endothelial cell density (range, 1055/mm 2 to 1655/mm 2). Both probands had a history of surgery for inguinal hernia; the male patient also reported hydrocele. CONCLUSIONS AND RELEVANCE Nucleotide changes within the coding region of ZEB1 underlie the pathogenesis of PPCD in 4 of 23 Czech probands (17%). The cumulative de novo ZEB1 mutation rate is at least 14%. Possible involvement of ZEB1 sequence variants not readily identified by direct sequencing of coding regions needs to be further investigated. Our findings also have implications for patient counseling.

show abstract

Immunohistochemical characterization of cytokeratins in the abnormal corneal endothelium of posterior polymorphous corneal dystrophy patients

Cited by 53 publications

References 24 publications

Heterozygous deletions at the ZEB1 locus verify haploinsufficiency as the mechanism of disease for posterior polymorphous corneal dystrophy type 3

Heterozygous deletions at the ZEB1 locus verify haploinsufficiency as the mechanism of disease for posterior polymorphous corneal dystrophy type 3

El citoesqueleto celular en la glándula mamaria y su aplicación diagnóstica

Further Genetic and Clinical Insights of Posterior Polymorphous Corneal Dystrophy 3

Contact Info

Product

Resources

About