Possible new complementation group of xeroderma pigmentosum

着色性干皮病（XP）是一种常染色体隐性光敏疾病，伴有异常的色素沉着和极高的皮肤癌发病率。XP患者的细胞对紫外线（UV）杀伤非常敏感，这与紫外线诱导的DNA损伤修复能力受损有关。遗传上存在7个核苷酸切除修复（NER）缺陷组（A~G）和一个NER精通型（XP变体）。这五年来，我们共收到348多份用于XP诊断的临床样本，我们实验室新诊断为XP的患者有108例。其中，我们发现了8例不寻常的日本XP病例。这些患者（17~55岁）没有相关性，有轻微的临床特征，暴露在阳光下的区域有少数皮肤癌，到目前为止还没有发现任何神经异常的证据。这些患者的成纤维细胞对紫外线照射的敏感性高于正常人，对紫外线的敏感性低于XP-A、XP-C和XP-D细胞，而这些患者的紫外线后非计划DNA合成（UDS）水平分别低于正常人的30%。通过细胞融合技术和质粒宿主细胞再激活实验进行互补试验，结果表明患者不属于XP a、B、C、D、F和g组。DNA修复研究和基因分析表明，患者不属于XP E组和XP变体。利用这些细胞株进行细胞融合分析，发现至少有两个新的XP互补群。cDNA和miRNA芯片分析显示，ATM、CLSPN和FANCD的表达降低。利用这些患者的细胞继续进行分子和生化分析，应该会对NER通路有新的认识。

Xeroderma pigmentosum (XP) is an autosomal recessive photosensitive disease with abnormal pigmentation and an extremely high incidence of skin cancers. Cells from patients with XP are hypersensitive to killing by ultraviolet (UV), which is associated with impaired ability to repair UV-induced DNA damages. There are genetically different seven nucleotide excision repair (NER) deficient groups (A～G) and a NER proficient form (XP variant). We have been receiving more than 348clinical samples for the diagnosis of XP for these five years and 108 patients were newly diagnosed as having XP in our laboratory. Among them, we found 8 unusual Japanese XP cases. Those patients (17～55 y.o.) are not related and have mild clinical features with a few skin cancers in areas exposed to sunlight and so far any evidence for neurological abnormalities was not detected. Fibroblasts derived from those patients were hypersensitive to UV irradiation compared to cells from normal subjects and less sensitive to UV than XP-A XP-C and XP-D cells, while the levels of post-UV unscheduled DNA synthesis (UDS) in those patients were less than 30% of normal, respectively. Complementation test by cell fusion technique and a plasmid host cell reactivation assay revealed that those patients did not belong to XP group A, B, C, D, F and G. DNA repair studies and gene analysis indicated that those patients were not in XP group E and XP variant. Cell fusion analysis using those cell strains implied that there were at least two more new XP complementation groups. cDNA and miRNA microarray analyses showed the decreased expression of ATM, CLSPN and FANCD. Continuing molecular and biochemical analyses using the cells from those patients should give a new insight in NER pathway.