A New, X-linked Endothelial Corneal Dystrophy
ABSTRACT To describe the clinical spectrum, the histopathologic findings obtained from one corneal button, and the genetic mapping of an X-linked endothelial corneal dystrophy (XECD).
Observational case series and experimental study.
We examined a total of 60 members of a family with this dystrophy at the slit-lamp. Light and electron microscopic findings of the corneal button were recorded following one male patient's penetrating keratoplasty. A panel of 25 microsatellite markers covering the X chromosome was typed in genomic DNA from 50 family members. The data were analyzed using the ALLEGRO program to obtain two-point and multipoint likelihood of the odds (LOD) scores and to generate haplotypes.
A total of 35 trait carriers were identified in four generations of the family. Nine male patients demonstrated severe corneal opacifications: two congenital corneal cloudings in form of ground glass, milky appearance and seven subepithelial band keratopathies combined with endothelial changes resembling moon craters. Twenty-two female and four male patients disclosed only endothelial alterations resembling moon craters. No instance of male-to-male transmission of the disease was encountered in the family. Light and electron microscopy disclosed focal discontinuities and degeneration of the endothelial cell layer and marked thickening of Descemet's membrane. Multipoint analysis showed linkage with a maximum LOD score of 10.90 between markers DXS8057 and DXS1047.
To the best of our knowledge, this represents the first fully documented report of X-linked inheritance of an endothelial corneal dystrophy. Late subepithelial band keratopathy is a landmark of XECD. A locus for this corneal dystrophy maps to Xq25.
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ABSTRACT: ■ Corneal dystrophies represent a highly heterogeneous group of hereditary disorders, consisting of more than 30 distinct entities, of which only 16 have their molecular basis partially or completely elucidated. The genetic characterization of corneal dystrophies revealed both genetic heterogeneity, i.e. different genes (KRT3 and KRT12) causing one single dystrophic phenotype, as well as phenotypic heterogeneity with one single gene (TGFBI) causing different dystrophic phenotypes (see below 5.5 keratoepithelinopathies).
Article: Corneal dystrophies.[Show abstract] [Hide abstract]
ABSTRACT: Corneal dystrophies are inherited (usually autosomal dominant) disorders involving virtually every layer of the cornea. They result in opacities of various sizes and shapes that primarily affect the central cornea relatively early in life. Diagnosis is most often based on clinical appearance and careful biomicroscopic examination to assess the corneal layer(s) that are affected. Because most dystrophies are slowly progressive, visual acuity is often minimally affected for much of an individual's lifetime. Dystrophies are not associated with any prior corneal inflammations or systemic disease. This paper is a discussion of the most commonly encountered dystrophies affecting the epithelium, Bowman's membrane, stroma, and endothelium. The optometric management of many of these dystrophies may, at times, present a challenge to the clinician. Treatment may range anywhere from a simple therapeutic contact lens to referral for penetrating keratoplasty.Optometry clinics: the official publication of the Prentice Society 02/1991; 1(4):31-44.
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ABSTRACT: The identification of the genetic basis of approximately half of the corneal dystrophies in the past decade has resulted in significant advances in our understanding of the genetic control of corneal clarity and has provided clinicians with a definitive means to confirm or refute presumptive clinical diagnoses. This article serves as a guide to understanding the genetic basis of the corneal dystrophies and provides a revised anatomically based classification system that is intended for the clinician, who must possess a working knowledge of the molecular genetic basis of the corneal dystrophies to accurately diagnose, counsel, and manage the disease in affected patients.Archives of Ophthalmology 03/2007; 125(2):177-86. DOI:10.1001/archopht.125.2.177 · 4.40 Impact Factor