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Clair-Florent Schmitt–Bernard, Caroline Guittard, Bernard Arnaud, Jacques Demaille, Angel Argiles, Mireille Claustres, Sylvie Tuffery–Giraud; BIGH3 Exon 14 Mutations Lead to Intermediate Type I/IIIA of Lattice Corneal Dystrophies. Invest. Ophthalmol. Vis. Sci. 2000;41(6):1302-1308.
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purpose. To screen the BIGH3 gene in three unrelated families
with lattice corneal dystrophy (LCD), two of which disclosed a
methods. Genomic DNA was extracted from peripheral leukocytes of the affected
patients and their family members. The entire coding sequence of the BIGH3 gene was screened for mutations by means of
transcript analysis on total RNA isolated from peripheral leukocytes by
reverse transcription–polymerase chain reaction performed with primers
designed for this study. Each mutation was confirmed at the genomic
level, by using published primers.
results. One family that had a typical form of LCD, had the described R124C
mutation in the BIGH3 gene. Two families with atypical
forms of LCD were negative for the previously known mutations of the
gene. Direct sequencing of the BIGH3 mRNA in the latter
two families allowed us to identify two mutations located in exon 14.
They consist of a 9-bp insertion at position 1885 1886 and
one missense mutation at position 1877 of the BIGH3 gene. Three new polymorphisms were also observed.
conclusions. Two mutations different from those linked to LCD have been found in
clinically distinguishable forms of this disease, intermediate between
LCDs types I and IIIA. The DNA segment comprising both alterations
normally encodes for a highly conserved region of the fourth internal
domain of the βig-h3 protein, suggesting that this region may be of
functional and/or structural importance. The identification of new
mutations by screening of the complete BIGH3 gene and
the comparative analysis of the induced modifications in βig-h3
protein should shed light in the understanding of the molecular
mechanisms underlying LCDs resulting from mutations in the BIGH3 gene, and may help to explain their phenotypic
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