Two novel mutations of TACSTD2 found in three Japanese gelatinous drop-like corneal dystrophy families with their aberrant subcellular localization.

Abstract

PURPOSE:

To report two novel mutation of the tumor-associated calcium signal transducer 2 (TACSTD2) gene in 3 Japanese patients with gelatinous drop-like corneal dystrophy (GDLD).

METHODS:

Genomic DNAs were extracted from the peripheral blood of 3 Japanese families. The coding region of TACSTD2 was amplified by polymerase chain reaction (PCR) and subjected to direct sequencing analysis. Plasmid vectors harboring normal and mutated TACSTD2 were transfected to the immortalized human corneal epithelial cells to identify the subcellular localization of the normal and mutated TACSTD2 gene products.

RESULTS:

Sequencing analysis of TACSTD2 revealed two novel homozygous mutations (c.840_841insTCATCATCGCCGGCCTCATC and c.675C>A which may result in frameshift (p.Ile281SerfsX23) and nonsense (p.Tyr225X) mutations, respectively) in the 3 GDLD patients. Protein expression analysis showed that the mutated gene product was distributed diffusely in the cytoplasm, whereas the normal gene product accumulated at the cell-to-cell borders.

CONCLUSIONS:

This study reports two novel mutations in 3 GDLD families and expands the spectrum of mutations in TACSTD2 that may cause pathological corneal amyloidosis.

• Authors: Mina Nakatsukasa, Satoshi Kawasaki, Kenta Yamasaki, Hideki Fukuoka, Akira Matsuda, Kohji Nishida, Shigeru Kinoshita
• Journal: Molecular vision (Mol Vis) Vol. 17 Pg. 965-70 (Apr 19 2011) ISSN: 1090-0535 [Electronic] United States
• PMID: 21541270 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Cell Adhesion Molecules
• Codon, Nonsense
• TACSTD2 protein, human

Topics

• Adult
• Aged
• Amyloidosis, Familial (genetics, pathology)
• Antigens, Neoplasm (chemistry, genetics)
• Asian People
• Base Sequence
• Cell Adhesion Molecules (chemistry, genetics)
• Cell Line, Transformed
• Codon, Nonsense (analysis)
• Cornea (metabolism, pathology)
• Corneal Dystrophies, Hereditary (genetics, pathology)
• Female
• Fluorescent Antibody Technique
• Frameshift Mutation
• Homozygote
• Humans
• Male
• Molecular Sequence Data
• Pedigree
• Plasmids
• Polymerase Chain Reaction
• Sequence Analysis, DNA
• Transfection