Méndez M, Poblete-Gutiérrez P, García-Bravo M, Wiederholt T, Morán-Jiménez M J, Merk H F, Garrido-Astray M C, Frank J, Fontanellas A, Enríquez de Salamanca R
Research Centre, University Hospital 12 de Octubre, Avda de Córdoba km 5.4, 28041 Madrid, Spain.
Br J Dermatol. 2007 Sep;157(3):501-7. doi: 10.1111/j.1365-2133.2007.08064.x. Epub 2007 Jul 11.
Porphyria cutanea tarda (PCT) results from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. In the majority of patients, the disease is sporadic (S-PCT or type I) and the enzyme deficiency is limited to the liver. Familial PCT (F-PCT or type II) is observed in 20-30% of patients in whom mutations on one allele of the UROD gene reduce UROD activity by approximately 50% in all tissues. Another variant of PCT (type III) is characterized by family history of the disease although it is biochemically indistinguishable from S-PCT.
To investigate the molecular basis of PCT in Spain and to compare enzymatic and molecular analysis for the identification of patients with F-PCT.
Erythrocyte UROD activity measurement and mutation analysis of the UROD gene were carried out in a cohort of 61 unrelated Spanish patients with PCT and 50 control individuals. Furthermore, each novel missense mutation identified was characterized by prokaryotic expression studies.
Of these 61 patients, 40 (66%) were classified as having S-PCT, 16 (26%) as having F-PCT and five (8%) as having type III PCT. Discordant results between enzymatic and molecular analysis were observed in two patients with F-PCT. In total, 14 distinct mutations were found, including 10 novel mutations: five missense, one nonsense, three deletions and an insertion. Prokaryotic expression of the novel missense mutations demonstrated that each results in decreased enzyme activity or stability.
These results confirm the high degree of molecular heterogeneity of F-PCT in Spain and emphasize the usefulness of molecular genetic analysis to distinguish between F-PCT and S-PCT.
迟发性皮肤卟啉病（PCT）是由于肝脏尿卟啉原脱羧酶（UROD）活性降低所致。在大多数患者中，该病为散发性（S-PCT或I型），酶缺乏仅限于肝脏。20% - 30%的患者存在家族性PCT（F-PCT或II型），其中UROD基因一个等位基因的突变会使所有组织中的UROD活性降低约50%。PCT的另一种变体（III型）的特点是有该病的家族史，尽管其在生化方面与S-PCT无法区分。
研究西班牙PCT的分子基础，并比较酶学分析和分子分析在识别F-PCT患者中的作用。
对61名无亲缘关系的西班牙PCT患者和50名对照个体进行了红细胞UROD活性测定及UROD基因突变分析。此外，对每个鉴定出的新错义突变进行原核表达研究以进行特征描述。
在这61名患者中，40名（66%）被归类为S-PCT，16名（26%）为F-PCT，5名（8%）为III型PCT。在两名F-PCT患者中观察到酶学分析和分子分析结果不一致。总共发现了14种不同的突变，包括10种新突变：5种错义突变、1种无义突变、3种缺失突变和1种插入突变。新错义突变的原核表达表明每种突变都会导致酶活性或稳定性降低。
这些结果证实了西班牙F-PCT的高度分子异质性，并强调了分子遗传学分析在区分F-PCT和S-PCT方面的有用性。
