MUTATIONS OF THE FUMARYLACETOACETATE HYDROLASE GENE IN 4 PATIENTS WITH TYROSINEMIA, TYPE-I

Tyrosinemia type I is an autosomal recessive inborn error of metabolis m caused by deficiency of the enzyme fumaryl acetoacetate hydrolase (F AH, EC 3.7.1.2.). We have used reverse transcription and the polymeriz e chain reaction to amplify the peptide coding region of the FAH cDNA from four patients with tyrosinemia type I. Chemical mismatch cleavage analysis and DNA sequencing were utilized to determine mutant alleles in all cases. A French Canadian patient was homozygous for a splice e rror mutation in the 3' portion of the gene. A second patient, from a consanguineous pedigree in Iran, had the identical splice alteration. The third patient has a missense mutation, changing valine to glycine in codon 166. And finally two nonsense mutations in codons 357 and 364 were found in the fourth patient.