MOLECULAR BIOLOGY OF HEREDITARY EYE DISEASES

Project: Research project

Project Details

Description

Ornithine Aminotransferase Deficiency in Gyrate Atrophy: Gyrate
atrophy (GA) is a blinding, autosomal recessive degenerative
disease of the retina and choroid of the eye characterized by a
generalized deficiency in the mitochondrial enzyme, ornithine
aminotransferase(OAT). Our molecular genetic investigation of this
disease has resulted in the cloning and characterization of a cDNA
for the human OAT, mapping of the OAT gene sequences to chromosomes
10 and X, identification of the OAT gene family and
characterization of the members of the family including the
functional OAT gene, construction of expression clones of OAT and
expression of OAT in heterologous tissues, and analysis of the OAT
gene and its expression in GA patients which has revealed a case
with a partial heterozygous deletion of the OAT gene and complete
absence of the OAT mRNA. By examining the family members of this
GA patient we were able to demonstrate the stable autosomal
recessive inheritance of the OAT gene and expression defect in the
family in addition to demonstrating the co-dominant mode of action
of the OAT gene. Analysis of a GA patient who shows a marked
decrease in the level of cellular OAT protein revealed that he is
expressing only one of the two alleles of the OAT gene and that the
expressed OAT contains a single point mutation resulting in an
amino acid change. This amino acid change appears to modify an
alpha-helical region of the OAT protein, and assay of the mutant
OAT protein for mitochondrial transport/processing seems to
indicate that the mutant protein fails to become processed.

Hereditary Retinoblastoma and X-linked Ocular Diseases: Work on
hereditary retinoblastoma is continuing with isolation of malignant
revertants of nonmalignant hybrids between Y79 retinoblastoma and
NIH3T3 cells and expression cloning of genes that may alter the
phenotype of retinoblastoma. A linkage of the OAT-related X
chromosome genes to Norrie Disease and X-linked retinitis
pigmentosa has been established using restriction fragment length
polymorphisms detected by the OAT probe.
StatusNot started

Funding

  • National Eye Institute
  • National Eye Institute

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