Identification of a combined missense/splice-site mutation in FAH causing tyrosinemia type 1

Tyrosinemia type I (HT1) is a genetic metabolic disorder characterized by progressive liver disease, kidney disease, and rickets. The disease is caused by mutations in the FAH gene that results in deficiency of fumarylacetoacetase, an enzyme that is involved in the tyrosine degradation pathway. We investigated the clinical characteristics and molecular cause of HT1 in an affected family from Iran. Molecular analysis identified a homozygous combined missense (c.G1009G>A, p.Gly337Ser) and aberrant splicing mutation removing the first 50 nucleotides of exon 12. This mutation was only described in HT1 patients from Scandinavian countries and this is the first report from another population. Although failure to thrive is one of the typical features in HT1, our proband, similar to the reported Scandinavian patients, had normal growth and development. The results of this study have applications in patient screening and genetic counselling.