摘要Background Mutations in fumarylacetoacetate hydrolase (FAH) gene can lead to tyrosinemia type 1 (HT1),a relatively rare autosomal recessive disorder.To date,no molecular genetic defects of HT1 in China have been described.We investigated a Chinese family with a HT1 child to identify mutations in FAH.Methods DNA sequencing was used for mutations screening in FAH gene.Real-time polymerase chain reaction (PCR) was performed to determine the FAH gene expression level.To confirm the presence of degradation by the nonsense-mediated mRNA decay pathway (NMD),the fragments containing R237X mutations were analyzed by primer introduced restriction analysis-polymerase chain reaction (PIRA-PCR) and cDNA sequencing.Finally,the effects of the mutations reported in this study were predicted by online softwares.Results A boy aged 3 years and 8 months was diagnosed clinically with HT1 based on his manifestations and biochemical abnormalities.Screening of FAH gene revealed two heterozygous mutations R237X and L375P transmitted from his mother and father respectively.In this pedigree,the amount of FAH mRNA relative to a healthy control was 0.44 for the patient,0.77 for his mother and 1.07 for his father.Moreover,both PIRA-PCR and cDNA sequencing showed significant reduction of the FAH mRNA with R237X nonsense mutation.The missense mutation of L375P was not reported previously and prediction software showed that this mutation decreased the stability of protein structure and affected protein function.Conclusions This is the first case of HT1 analyzed by molecular genetics in China.The R237X mutation in FAH downregulates the FAH gene expression,and the L375P mutation perhaps interrupts the secondary structure of FAH protein.