Porphyria Cutanea Tarda (PCT) is a cutaneous porphyria that results from the hepatic inhibition of the heme biosynthetic enzyme uroporphyrinogen decarboxylase (UROD), and can occur either in the absence or presence of an inherited heterozygous UROD mutation (PCT subtypes 1 and 2, respectively). A heterozygous UROD mutation causes half-normal levels of UROD activity systemically, which is a susceptibility factor but is not sufficient alone to cause type 2 PCT. In both Types 1 and 2 PCT, the cutaneous manifestations are precipitated by additional factors that lead to generation of an inhibitor that more profoundly reduces hepatic UROD activity. PCT is an iron-related disorder, and many of its known susceptibility factors, which include infections (e.g. hepatitis C virus, HIV), high alcohol consumption, smoking, estrogens, and genetic traits (e.g. hemochromatosis mutations) can increase hepatic iron accumulation. Hepatoerythropoietic Porphyria (HEP) is a rare autosomal recessive disease that results from homozygosity or compound heterozygosity for UROD mutations and often causes infantile or childhood onset of both erythropoietic and cutaneous manifestations. During the 11-year period from 01/01/2007 through 12/31/2017, the Mount Sinai Porphyrias Diagnostic Laboratory provided molecular diagnostic testing for 387 unrelated patients with PCT and four unrelated patients with HEP. Of the 387 unrelated individuals tested for Type 2 PCT, 79 (20%) were heterozygous for UROD mutations. Among 26 family members of mutation-positive PCT patients, eight (31%) had the respective family mutation. Additionally, of the four unrelated HEP patients referred for UROD mutation analyses, all had homozygosity or compound heterozygosity for UROD mutations, and all eight asymptomatic family members were heterozygotes for UROD mutations. Of the UROD mutations identified, 19 were novel, including nine missense, two nonsense, one consensus splice-site, and seven insertions and deletions. These results expand the molecular heterogeneity of PCT and HEP by adding a total of 19 novel UROD mutations. Moreover, the results document the usefulness of molecular testing to confirm a genetic susceptibility trait in Type 2 PCT, confirm a diagnosis in HEP, and identify heterozygous family members.

中文翻译：

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角卟啉卟啉菌和肝造血卟啉症：鉴定19个新的尿卟啉原III脱羧酶突变。

Porphyria Cutanea Tarda（PCT）是一种皮肤卟啉症，是由肝抑制血红素生物合成酶尿卟啉原脱羧酶（UROD）产生的，可以在不存在或存在遗传杂合性UROD突变的情况下发生（分别为PCT亚型1和2） ）。杂合的UROD突变会全身性地引起UROD活性的一半正常水平，这是易感性因素，但不足以单独引起2型PCT。在1型和2型PCT中，皮肤表现都是由其他因素引起的，这些因素导致生成抑制剂，从而更深刻地降低肝脏UROD活性。PCT是一种与铁有关的疾病，其许多已知的易感性因素包括感染（例如丙型肝炎病毒，HIV），酗酒，吸烟，雌激素和遗传特征（例如 血色素沉着病突变）可以增加肝铁的积累。肝造血卟啉症（HEP）是一种罕见的常染色体隐性遗传疾病，由UROD突变的纯合性或复合杂合性引起，通常导致婴儿或儿童期红细胞生成和皮肤表现。在2007年1月1日至2017年12月31日的11年中，西奈山卟啉病诊断实验室为387名PCT无关患者和4名HEP无关患者提供了分子诊断检测。在为2型PCT测试的387名无关个体中，有79名（20％）是UROD突变的杂合子。在26位突变阳性PCT患者的家庭成员中，有8位（31％）具有各自的家庭突变。此外，在四名不相关的HEP患者中，他们接受了UROD突变分析，所有这些都具有UROD突变的纯合或复合杂合性，并且所有8个无症状家族成员都是UROD突变的杂合子。在鉴定出的UROD突变中，有19个是新颖的，包括9个错义，2个无意义，1个共有剪接位点和7个插入和缺失。这些结果通过添加总共19个新的UROD突变扩大了PCT和HEP的分子异质性。此外，结果证明了分子检测对确认2型PCT的遗传易感性，确认HEP的诊断以及鉴定杂合家族成员的有用性。以及七个插入和删除。这些结果通过添加总共19个新的UROD突变扩大了PCT和HEP的分子异质性。此外，结果证明了分子检测对确认2型PCT的遗传易感性，确认HEP的诊断以及鉴定杂合家族成员的有用性。以及七个插入和删除。这些结果通过添加总共19个新的UROD突变扩大了PCT和HEP的分子异质性。此外，结果证明了分子检测对确认2型PCT的遗传易感性，确认HEP的诊断以及鉴定杂合家族成员的有用性。