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A Novel Variant of Granular Corneal Dystrophy Caused by Association of 2 Mutations in the TGFBI Gene—R124L and T125-E126

Paul Dighiero, MD; Séverine Drunat, MD; François D'Hermies, MD; Gilles Renard, MD; Marc Delpech, MD, PhD; Sophie Valleix, MD, PhD

Arch Ophthalmol. 2000;118:814-818.

Objective  To characterize the molecular defect in the TGFBI gene in a French family affected with an atypical granular corneal dystrophy.

Patients  This family comprises 9 affected individuals across 3 generations without consanguineous marriage.

Methods  Light and electron microscopy were used to examine corneal buttons from patients. Exons of the TGFBI gene were amplified by polymerase chain reaction and sequenced directly using an automated method. Restriction digestion analysis and heteroduplex screening were performed to confirm that the mutations identified were not polymorphisms.

Results  Round or snowflakes-like deposits that stained red with Masson trichrome and appeared as dense, rod-shaped structures were observed in the most anterior layers of the central stroma. All patients were heterozygous for the R124L mutation and a novel mutation predicting the deletion of 2 amino acid residues—threonine (T) and glutamic acid (E)—at codons 125 and 126.

Conclusions  This French family is affected with a novel variant of granular dystrophy that is caused by a molecular defect in the TGFBI gene, reported here for the first time.

Clinical Relevance  These 2 mutations cause a novel variant of granular dystrophy that is intermediate in severity between the classical and superficial variant forms.

From the Department of Ophthalmology, Hôtel-Dieu Hospital (Drs Dighiero, D'Hermies, and Renard), and the Laboratoire de Biochimie et Génétique Moléculaire (Drs Drunat, Delpech, and Valleix), Paris, France.

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