Point mutations in the tyrosine aminotransferase gene in tyrosinemia type II

Ernst Natt, Kaichi Kida, Michele Odievre, Maja Di Rocco, Gerd Scherer

Research output: Contribution to journalArticlepeer-review


Tyrosinemia type II (Richner-Hanhart syndrome, RHS) is a disease of autosomal recessive inheritance characterized by keratitis, palmoplantar hyperkeratosis, mental retardation, and elevated blood tyrosine levels. The disease results from deficiency in hepatic tyrosine aminotransferase (TAT; L-tyrosine:2-oxoglutarate aminotransferase, EC, a 454-amino acid protein encoded by a gene with 12 exons. To identify the causative mutations in five TAT alleles cloned from three RHS patients, chimeric genes constructed from normal and mutant TAT alleles were tested in directing TAT activity in a transient expression assay. DNA sequence analysis of the regions identified as nonfunctional revealed six different point mutations. Three RHS alleles have nonsense mutations at codons 57, 223, and 417, respectively. One "complex" RHS allele carries a GT → GG splice donor mutation in intron 8 together with a Gly → Val substitution at amino acid 362. A new splice acceptor site in intron 2 of the fifth RHS allele leads to a shift in reading frame.

Original languageEnglish
Pages (from-to)9297-9301
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number19
Publication statusPublished - Oct 1 1992


  • Complex allele
  • Inborn error of metabolism
  • Richner-Hanhart syndrome
  • Splice mutation

ASJC Scopus subject areas

  • Genetics
  • General


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