Novel mutation of FAH gene identified from a patient with acute hereditary tyrosinemia type Ⅰ

Abstract

FAH (fumarylacetoacetate hydrolase) is the last enzyme of tyrosine degradation pathway which catalyzes the hydrolysis of fumarylacetoacetate to fumarate and acetoacetate. Tyrosinemia Type1 (HT1) is the disease caused by the defect of this enzyme and is transmitted by autosomal recessive manner. Kim O O was the patient who showed typical acute type HT1 symptoms and died at the age of eight months after birth. Through the methods of molecular biological techniques, this acute HT1 patient was investigated. Fourteen exons of the patient``s and his parents`` FAH gene were enzymatically amplified and sequenced. Two missense mutations were found. One was Pro to Leu in exon 9 which came from the maternal side, and the other was Phe to Ser in exon 8 which came from paternal side. These two missense mutations seemed to be responsible for the deficiency of functional FAH proteins.