Abstract: Gelatinous drop–like corneal dystrophy (GDLD) is a rare autosomal recessive disorder, clinically characterized by grayish corneal deposits of amyloid and by severely impaired visual acuity. Most patients require corneal transplantation. We identified the gene responsible for GDLD, tumor-associated calcium signal transducer 2 (TACSTD2), by positional cloning and detected 4 disease-causing mutations in Japanese patients with GDLD. During the positional cloning process, strong linkage disequilibrium was observed between GDLD and some markers in the critical region. More than 90% of GDLD patients possessed the same haplotype with a Q118X mutation in TACSTD2. This may be the result of a founder effect and reflects that most GDLD patients are Japanese. TACSTD2 deleterious mutations resulted in destabilized tight junction proteins, including claudins, ZO-1, and occludin. These findings may explain why the corneal epithelium barrier function is impaired in GDLD patients.
Department of Ophthalmology, Osaka University Medical School, Osaka, Japan.
Reprints: Motokazu Tsujikawa, Department of Ophthalmology, Osaka University School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Osaka, Japan (e-mail: firstname.lastname@example.org).
Supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology (No. 21592229) and from the Ministry of Health, Labour and Welfare (No. 11103544).
The author has no conflicts of interest, financial or otherwise, to declare.