PMID- 10192395
OWN - NLM
STAT- MEDLINE
DCOM- 19990426
LR  - 20161124
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 21
IP  - 4
DP  - 1999 Apr
TI  - Identification of the gene responsible for gelatinous drop-like corneal
      dystrophy.
PG  - 420-3
AB  - 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 interval on chromosome
      1p. 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.
FAU - Tsujikawa, M
AU  - Tsujikawa M
AD  - Department of Medical Genetics, Biomedical Research Center, Osaka University
      Medical School, Japan.
FAU - Kurahashi, H
AU  - Kurahashi H
FAU - Tanaka, T
AU  - Tanaka T
FAU - Nishida, K
AU  - Nishida K
FAU - Shimomura, Y
AU  - Shimomura Y
FAU - Tano, Y
AU  - Tano Y
FAU - Nakamura, Y
AU  - Nakamura Y
LA  - eng
SI  - GENBANK/P06396
SI  - GENBANK/U33055
SI  - GENBANK/X13425
SI  - GENBANK/X77753
SI  - GENBANK/Y08830
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Epithelial Cell Adhesion Molecule)
RN  - 0 (Genetic Markers)
RN  - 0 (Phosphatidylinositol 4,5-Diphosphate)
RN  - 0 (Recombinant Proteins)
SB  - IM
MH  - Amyloidosis/*genetics
MH  - Animals
MH  - Antigens, Neoplasm/*genetics/metabolism
MH  - Binding Sites
MH  - COS Cells/metabolism
MH  - Cell Adhesion Molecules/*genetics/metabolism
MH  - Cloning, Molecular
MH  - Corneal Dystrophies, Hereditary/*genetics
MH  - Epithelial Cell Adhesion Molecule
MH  - Female
MH  - Genetic Markers
MH  - HeLa Cells/metabolism
MH  - Homozygote
MH  - Humans
MH  - Japan
MH  - Linkage Disequilibrium
MH  - Male
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Phosphatidylinositol 4,5-Diphosphate/metabolism
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Restriction Fragment Length
MH  - Recombinant Proteins/genetics/metabolism
MH  - Sequence Analysis
EDAT- 1999/04/07 02:01
MHDA- 2001/03/23 10:01
CRDT- 1999/04/07 02:01
PHST- 1999/04/07 02:01 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/04/07 02:01 [entrez]
AID - 10.1038/7759 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Apr;21(4):420-3. doi: 10.1038/7759.