Chromosomal sharing in atypical cases of gelatinous drop-like corneal dystrophy

To present the phenotypic variability both among and within families in Japanese gelatinous drop-like corneal dystrophy (GDLD), and to study the genetic background of the variability.

Four Japanese families who suffer from bilateral corneal amyloidoses were studied by a molecular genetic method. All families included a patient whose clinical features alone could not be used to diagnose GDLD. In one family, obvious clinical differences were observed between the two members who were patients. Three families had members who suffered from atypical amyloidoses that had not been initially diagnosed as GDLD. For their final diagnoses and for the investigation of the genetic background of these phenotypes, the sequences of the entire TACSTD2 gene and the genotypes of some polymorphic markers close to the TACSTD2 gene were studied.

Genetic analysis revealed that all the patients possessed a homozygous Q118X mutation in TACSTD2, a major founder mutation in Japanese GDLD. There were no differences in the entire sequence of TACSTD2 in these patients compared with other GDLD patients. Moreover, the genotyping of polymorphic markers near the TACSTD2 gene revealed that these patients shared the same founder chromosome as well as the TACSTD2 gene.

In Japanese GDLD patients, phenotypic variability is observed both among and within families in spite of the allelic homogeneity of Q118X. Even in these atypical cases, the patients shared the same chromosomal region, received from a founder.