Congenital stromal dystrophy of the cornea caused by a mutation in the decorin gene.
OBJECTIVE
To describe the clinical and pathologic characteristics of a family with a congenital stromal dystrophy of the cornea and to identify the genetic basis for this disorder.


METHODS
All family members in three generations underwent ophthalmic examination. Stored corneal buttons were examined by transmission electron microscopy. Molecular genetic studies, including a genome-wide scan with microsatellite markers, linkage analysis, and DNA sequencing, were performed.


RESULTS
The dystrophy was inherited in an autosomal dominant pattern and was seen as clouded corneas shortly after birth. No associated systemic abnormalities or congenital diseases were present. After penetrating keratoplasty (PK), the grafts remained completely clear in 56% of the eyes with a mean (range) observation period of 19.5 years (3-36). Transmission electron microscopy of corneal buttons revealed lamellae with normal arrangement of collagen fibrils separated by abnormal fibrillar layers. Genome-wide screening revealed linkage to chromosome 12q22, with a maximum LOD score of 4.68 at D12S351. Subsequent sequencing of candidate genes revealed a frameshift mutation in the DCN gene (c.967delT) that encodes for decorin, predicting a C-terminal truncation of the decorin protein (p.S323fsX5).


CONCLUSIONS
The authors hypothesize that truncated decorin binds to collagen in a suboptimal way, disturbing the regularity of corneal collagen fibril formation and thereby causing corneal opacities. To the best of the authors' knowledge, this is the first description of a disorder associated with an inherited alteration in the decorin gene in humans.
Bredrup
Cecilie
C
Section of Ophthalmology, Department of Clinical Medicine, University of Bergen, Norway.
Knappskog
Per M
PM
Majewski
Jacek
J
Rødahl
Eyvind
E
Boman
Helge
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003317:Corneal Dystrophies, Hereditary / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D003318:Corneal Opacity / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D003319:Corneal Stroma / Q000648:ultrastructure*; D004252:DNA Mutational Analysis; D058575:Decorin; D016326:Extracellular Matrix Proteins; D005260:Female; D016368:Frameshift Mutation; D005799:Genes, Dominant; D008040:Genetic Linkage; D005838:Genotype; D006801:Humans; D015948:Keratoplasty, Penetrating; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D018613:Microscopy, Confocal; D008875:Middle Aged; D010375:Pedigree; D011509:Proteoglycans / Q000235:genetics*
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans