Identification of the gene responsible for gelatinous drop-like corneal dystrophy

Motokazu Tsujikawa, Hiroki Kurahashi, Toshihiro Tanaka, Kohji Nishida, Yoshikazu Shimomura, Yasuo Tano, Yusuke Nakamura

Research output: Contribution to journalArticle

135 Citations (Scopus)

Abstract

Gelatinous drop-like corneal dystrophy (GDLD; OMIM 204870) is an autosomal recessive disorder characterized by severe corneal amyloidosis leading to blindness, with an incidence of 1 in 300,000 in Japan. Our previous genetic linkage study localized the gene responsible to a 2.6-cM internal on chromosome 1p (ref. 6). Clinical manifestations, which appear in the first decade of life, include blurred vision, photophobia and foreign- body sensation. By the third decade, raised, yellowish-grey, gelatinous masses severely impair visual acuity, and lamellar keratoplasty is required for most patients. Here we report DNA sequencing, cDNA cloning and mutational analyses of four deleterious mutations (Q118X, 632delA, Q207X and S170X) in M1S1 (formerly TROP2 and GA733-1), encoding a gastrointestinal tumour- associated antigen. The Q118X mutation was the most common alteration in the GDLD patients examined, accounting for 33 of 40 (82.5%) disease alleles in our panel of families. Protein expression analysis revealed aggregation of the mutated, truncated protein in the perinuclear region, whereas the normal protein was distributed diffusely in the cytoplasm with a homogenous or fine granular pattern. Our successful identification of the gene that is defective in GDLD should facilitate genetic diagnosis and potentially treatment of the disease, and enhance general understanding of the mechanisms of amyloidosis.

Original languageEnglish
Pages (from-to)420-423
Number of pages4
JournalNature Genetics
Volume21
Issue number4
DOIs
Publication statusPublished - 01-04-1999

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Genes
Genetic Databases
Photophobia
Mutation
Proteins
Genetic Linkage
Corneal Transplantation
Neoplasm Antigens
Amyloidosis
Blindness
Foreign Bodies
DNA Sequence Analysis
Visual Acuity
Organism Cloning
Japan
Cytoplasm
Complementary DNA
Chromosomes
Alleles
Incidence

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

Tsujikawa, M., Kurahashi, H., Tanaka, T., Nishida, K., Shimomura, Y., Tano, Y., & Nakamura, Y. (1999). Identification of the gene responsible for gelatinous drop-like corneal dystrophy. Nature Genetics, 21(4), 420-423. https://doi.org/10.1038/7759
Tsujikawa, Motokazu ; Kurahashi, Hiroki ; Tanaka, Toshihiro ; Nishida, Kohji ; Shimomura, Yoshikazu ; Tano, Yasuo ; Nakamura, Yusuke. / Identification of the gene responsible for gelatinous drop-like corneal dystrophy. In: Nature Genetics. 1999 ; Vol. 21, No. 4. pp. 420-423.
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Tsujikawa, M, Kurahashi, H, Tanaka, T, Nishida, K, Shimomura, Y, Tano, Y & Nakamura, Y 1999, 'Identification of the gene responsible for gelatinous drop-like corneal dystrophy', Nature Genetics, vol. 21, no. 4, pp. 420-423. https://doi.org/10.1038/7759

Identification of the gene responsible for gelatinous drop-like corneal dystrophy. / Tsujikawa, Motokazu; Kurahashi, Hiroki; Tanaka, Toshihiro; Nishida, Kohji; Shimomura, Yoshikazu; Tano, Yasuo; Nakamura, Yusuke.

In: Nature Genetics, Vol. 21, No. 4, 01.04.1999, p. 420-423.

Research output: Contribution to journalArticle

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AU - Tanaka, Toshihiro

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AU - Shimomura, Yoshikazu

AU - Tano, Yasuo

AU - Nakamura, Yusuke

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