Limbal Stem Cell Deficiency and Ocular Phenotype in Ectrodactyly-Ectodermal Dysplasia-Clefting Syndrome Caused by p63 Mutations
| Autor: | Giuseppe Castaldo, Vanessa Barbaro, John A. McGrath, Diego Ponzin, Elisabetta Böhm, Paola Nardiello, Enzo Di Iorio, Stephen B. Kaye, Colin E. Willoughby, Stefano Ferrari |
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| Přispěvatelé: | Di Iorio, E, Kaye, Sb, Ponzin, D, Barbaro, V, Ferrari, S, Böhm, E, Nardiello, P, Castaldo, Giuseppe, Mcgrath, Ja, Willoughby, Ce |
| Rok vydání: | 2012 |
| Předmět: |
Male
Pathology Ectodermal dysplasia Ectrodactyly genetic structures DNA Mutational Analysis Visual Acuity Meibomian gland Polymerase Chain Reaction Corneal Diseases Ectodermal Dysplasia Missense mutation Limbal stem cell Child Fluorescent Antibody Technique Indirect Stem Cells Epithelium Corneal Middle Aged Cleft Palate limbal stem cell deficiency LSCD Phenotype medicine.anatomical_structure Child Preschool Immunohistochemistry Adult medicine.medical_specialty Adolescent Cleft Lip Mutation Missense Vision Disorders p63 sequence variants Limbus Corneae Ophthalmology medicine Humans Retrospective Studies ectrodactyly ectodermal dysplasia clefting EEC syndrome business.industry Tumor Suppressor Proteins Epithelial Cells Retrospective cohort study medicine.disease eye diseases stomatognathic diseases Histopathology sense organs business Keratoplasty Penetrating Transcription Factors |
| Zdroj: | Ophthalmology. 119:74-83 |
| ISSN: | 0161-6420 |
| DOI: | 10.1016/j.ophtha.2011.06.044 |
| Popis: | Objective To describe the ocular phenotype in patients with ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome (MIM#604292) and to determine the pathogenic basis of visual morbidity. Design Retrospective case series. Participants Nineteen families (23 patients) affected by EEC syndrome from the United Kingdom, Ireland, and Italy. Methods General medical examination to fulfill the diagnostic criteria for EEC syndrome and determine the phenotypic severity. Mutational analysis of p63 was performed by polymerase chain reaction–based bidirectional Sanger sequencing. All patients with EEC syndrome underwent a complete ophthalmic examination and ocular surface assessment. Limbal stem cell deficiency (LSCD) was diagnosed clinically on the basis of corneal conjunctivalization and anatomy of the limbal palisades of Vogt. Impression cytology using immunofluorescent antibodies was performed in 1 individual. Histologic and immunohistochemical analyses were performed on a corneal button and corneal pannus from 2 EEC patients. Main Outcome Measures The EEC syndrome phenotypic severity (EEC score), best-corrected Snellen visual acuity (decimal fraction), slit-lamp biomicroscopy, tear function index, tear breakup time, LSCD, p63 DNA sequence variants, impression cytology, and corneal histopathology. Results Eleven heterozygous missense mutations in the DNA binding domain of p63 were identified in all patients with EEC syndrome. All patients had ocular involvement and the commonest was an anomaly of the meibomian glands and lacrimal drainage system defects. The major cause of visual morbidity was progressive LSCD, which was detected in 61% (14/23). Limbal stem cell deficiency was related to advancing age and caused a progressive keratopathy, resulting in a dense vascularized corneal pannus, and eventually leading to visual impairment. Histologic analysis and impression cytology confirmed LSCD. Conclusions Heterozygous p63 mutations cause the EEC syndrome and result in visual impairment owing to progressive LSCD. There was no relationship of limbal stem cell failure with the severity of EEC syndrome, as classified by the EEC score, or the underlying molecular defect in p63 . Financial Disclosure(s) The authors have no proprietary or commercial interest in any of the materials discussed in this article. |
| Databáze: | OpenAIRE |
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