Variegate porphyria (VP) is an autosomal-dominant disorder that is caused by 
inheritance of a partial deficiency of the enzyme protoporphyrinogen oxidase (EC 
1.3.3.4). It is characterized by cutaneous photosensitivity and/or various 
neurological manifestations. Protoporphyrinogen oxidase catalyses the 
penultimate step of haem biosynthesis, and mutations in the PPOX gene have been 
coupled to VP. In the present study, sequencing analysis revealed 10 different 
mutations in the PPOX gene in 14 out of 17 apparently unrelated Swedish VP 
families. Six of the identified mutations, 3G > A (exon 2), 454C > T (exon 5), 
472G > C (exon 6), 614C > T (exon 6), 988G > C (exon 10) and IVS12 + 2T > G 
(intron 12), are single nucleotide substitutions, while 604delC (exon 6), 
916-17delCT (exon 9) and 1330-31delCT (exon 13) are small deletions, and IVS12 + 
2-3insT (intron 12) is a small insertion. Only one of these 10 mutations has 
been reported previously. Three of the mutations were each identified in two or 
more families, while the remaining mutations were specific for an individual 
family. In addition to the 10 mutations, one previously unreported single 
nucleotide polymorphism was identified. Mutation analysis of family members 
revealed two adults and four children who were silent carriers of the VP trait. 
Genetic analysis can now be added to the conventional biochemical analyses and 
used in investigation of putative carriers of a VP trait in these families.