McManus J F, Begley C G, Sassa S, Ratnaike S
Department of Biochemistry, P.O. Royal Melbourne Hospital, Victoria, Australia.
Hum Mutat. 1999;13(5):412. doi: 10.1002/(SICI)1098-1004(1999)13:5<412::AID-HUMU13>3.0.CO;2-N.
We have characterised three new mutations in the uroporphyrinogen decarboxylase gene in familial porphyria cutanea tarda. The first of these was a G to A substitution in the 5' splice junction of exon 4 which generated an mRNA that lacked exon 4. The second was a nonsense mutation in exon 5 which changed the arginine residue at position 142 to a stop codon, and the third mutation, also in exon 5, was a triple base substitution from nucleotide position 417 to 419. This mutation encompassed two codons but only changed the amino acid predicted from the second codon, resulting in the replacement of valine with glutamine at position 134. This missense mutation has been described previously by Meguro et al. 1994, on one allele in a compound heterozygote with hepatoerythropoietic porphyria. This is the third case of an hepatoerythropoietic porphyria mutation in an individual diagnosed with familial porphyria cutanea tarda.
我们已鉴定出迟发性皮肤卟啉病家族中尿卟啉原脱羧酶基因的三个新突变。其中第一个是外显子4的5'剪接位点处的G到A替换，产生了一个缺少外显子4的mRNA。第二个是外显子5中的无义突变，将第142位的精氨酸残基变为终止密码子，第三个突变也在外显子5中，是从核苷酸位置417到419的三碱基替换。该突变包含两个密码子，但仅改变了第二个密码子预测的氨基酸，导致第134位的缬氨酸被谷氨酰胺取代。这种错义突变先前已被Meguro等人于1994年在一名患有肝红细胞生成性卟啉病的复合杂合子的一个等位基因上描述过。这是在被诊断为迟发性皮肤卟啉病家族的个体中出现肝红细胞生成性卟啉病突变的第三例。
