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Hideki Fukuoka, Satoshi Kawasaki, Kenta Yamasaki, Akira Matsuda, Akiko Fukumoto, Akira Murakami, Shigeru Kinoshita; Lattice Corneal Dystrophy Type IV (p.Leu527Arg) Is Caused by a Founder Mutation of the TGFBI Gene in a Single Japanese Ancestor. Invest. Ophthalmol. Vis. Sci. 2010;51(9):4523-4530. doi: 10.1167/iovs.10-5343.
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Lattice corneal dystrophy (LCD) type IV (LCD4) is a late-onset corneal dystrophy with amyloid deposition at the deep stromal layer of cornea. As with other corneal dystrophies, this LCD subtype is also caused by a mutation (p. Leu527Arg) of the transforming growth factor, β-induced (TGFBI) gene. Although LCD type I has been reported worldwide, LCD4 has been reported only in the Japanese population. In the present study, a haplotype analysis was performed to investigate whether this LCD subtype is caused by a founder mutation.
Genomic DNA samples were extracted from 13 unrelated patients with LCD4. As a control, genomic DNA samples from 96 normal volunteers were also analyzed. For the haplotype analysis, the samples were amplified by polymerase chain reaction (PCR), TA-cloned, isothermally amplified, and subjected to a 1-base primer extension assay against a mutation site (c.1580T>G) and six known single-nucleotide polymorphisms (SNPs; rs4669, rs2072239, rs7727725, rs17689879, rs6871571, and rs3792900), which are located adjacent to the mutation site.
The haplotype analysis revealed that all the disease-carrying alleles from the 13 LCD4 patients shared an identical haplotype, whereas non–disease-carrying alleles from the normal volunteers and the LCD4 patients exhibited four haplotypes. There was a statistically significant difference in the haplotype distribution between the disease-carrying and the non–disease-carrying alleles.
The findings of this study strongly indicate that LCD4 was caused by a founder mutation of the TGFBI gene that occurred in a single Japanese ancestor.
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