Molecular epidemiology of erythropoietic protoporphyria in the UK
Molecular epidemiology of erythropoietic protoporphyria in the UK
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DOI：
10.1111/j.1365-2133.2010.09631.x
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发表时间：
2010-03-01
影响因子：
10.3
通讯作者：
Badminton, M. N.
中科院分区：
文献类型：
--
作者：
Whatley, S. D.;Mason, N. G.;Badminton, M. N.
红细胞生成性原卟啉症（EPP）是一种由铁螯合酶（FECH）突变引起的皮肤卟啉症，或者较少发生的是氨基乙酰酸合酶2 （ALAS2）基因突变。预测性遗传咨询需要准确的分子诊断和遗传模式的知识。目的探讨EPP在英国的分子流行病学特点。方法对191例英国无亲属关系的EPP患者的DNA样本进行FECH和ALAS2基因突变和FECH IVS3-48二态性分析。结果179例（94%）患者发现突变。大多数（169例，94%）在一个等位基因上有FECH突变，并被归类为假显性EPP (psdEPP)；7例（4%）患者在两个等位基因上都有FECH突变（常染色体隐性EPP）， 3例（2%）患者有ALAS2突变（x连锁显性原卟啉症）。FECH IVS3-48C等位基因与psdp密切相关，并且与FECH或ALAS2位点的突变缺失密切相关。鉴定出56个FECH突变，其中19个以前未报道。错义突变在常染色体隐性EPP中占主导地位（82%），而在ps德普中不占主导地位（32%）。在41个（24%）EPP家族中存在一个突变（c. 314 + 2T>G），其中大多数似乎来自居住在英格兰北部的共同祖先。结论这些数据明确了EPP在英国的患病率和分子流行病学。
Background Erythropoietic protoporphyria (EPP) is a cutaneous porphyria caused by mutations in the ferrochelatase (FECH) or, less frequently, the delta-aminolaevulinate synthase 2 (ALAS2) gene. Predictive genetic counselling requires accurate molecular diagnosis and knowledge of patterns of inheritance.Objectives To investigate the molecular epidemiology of EPP in the U. K.Methods DNA samples from 191 unrelated patients resident in the U. K. were analysed for mutations in the FECH and ALAS2 genes and for the FECH IVS3-48 dimorphism.Results Mutations were identified in 179 (94%) patients. Most (169; 94%) had a FECH mutation on one allele and were classified as having pseudodominant EPP (psdEPP); seven (4%) patients had FECH mutations on both alleles (autosomal recessive EPP) and three (2%) patients had ALAS2 mutations (X-linked dominant protoporphyria). The FECH IVS3-48C allele was strongly associated with psdEPP and with the absence of mutations at the FECH or ALAS2 loci. Fifty-six FECH mutations were identified, 19 being previously unreported. Missense mutations were predominant in autosomal recessive EPP (82%) but not in psdEPP (32%). One mutation (c. 314 + 2T>G) was present in 41 (24%) of EPP families, most of whom appeared to be descended from a common ancestor resident in the north of England.Conclusions These data define the prevalence and molecular epidemiology of each type of EPP in the U. K.