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Genetics of the corneal endothelial dystrophies: an evidence‐based review
Author(s) -
Aldave A J,
Han J,
Frausto R F
Publication year - 2013
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12191
Subject(s) - genetics , corneal endothelium , locus (genetics) , biology , corneal dystrophy , dystrophy , gene , genetic linkage , endothelium , cornea , neuroscience
The aim of this review was to provide an evidenced‐based review of the genetic basis of the corneal endothelial dystrophies. A review of the English language peer‐reviewed literature describing the molecular genetic basis of posterior polymorphous corneal dystrophy ( PPCD ), congenital hereditary endothelial dystrophy ( CHED ), Fuchs endothelial corneal dystrophy ( FECD ) and X‐linked endothelial corneal dystrophy ( XECD ) was performed. Mutations in several genes have been implicated as playing a pathogenic role in the corneal endothelial dystrophies: VSX1 mutations in PPCD1 ; COL8A2 mutations in PPCD2 and FECD ; ZEB1 mutations in PPCD3 and FECD ; and SLC4A11 mutations in CHED2 and FECD . However, linkage, association and familial segregation analyses support a role of only one gene in each corneal endothelial dystrophy: ZEB1 in PPCD3 , SLC4A11 in CHED2 and COL8A2 in FECD (early onset). In addition, insufficient evidence exists to consider the autosomal dominant form of CHED ( CHED1 ) as distinct from PPCD . An accurate classification of the corneal endothelial dystrophies requires a critical review of the evidence to support the role of each suggested chromosomal locus, gene and genetic mutation associated with a corneal endothelial dystrophy. Only after the separation of evidence from opinion is performed can a critical examination of the molecular pathways that lead to endothelial dysfunction in each of these disorders be accurately performed.