A ten-year follow up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole genome sequencing.
A ten-year follow up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole genome sequencing.
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对一名通过全基因组测序诊断为 D 组轻度着色性干皮病的儿童进行了为期 10 年的随访。
DOI：
10.1111/phpp.12240
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Nishigori C.
中科院分区：
文献类型：
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作者：
Ono R;Masaki T;Mayca Pozo F;Nakazawa Y;Swagemakers SM;Nakano E;Sakai W;Takeuchi S;Kanda F;Ogi T;van der Spek PJ;Sugasawa K;Nishigori C.
背景西方国家的着色性干皮病互补D组（XP-D）患者大多数患有神经系统症状，而日本患者仅表现出皮肤表现而没有神经系统症状。我们以前曾建议，这些差异在XP‐D患者的临床表现部分归因于一个主要的突变inERCC 2，和等位基因频率S541 R是最高的在Japanes.MethodsWe诊断为轻度病例XP‐D的DNA修复活性和全基因组测序的评估，并遵循她十years.ResultsSkin cancer，精神发育迟滞，神经系统症状没有观察到。她的最小红斑剂量为41 mJ/cm 2，略低于日本健康志愿者。与正常细胞相比，患者的细胞对紫外线表现出六倍的超敏性。未照射样本的UV后非程序DNA合成率为20.4%，UV后RNA合成恢复率为58%，低于正常成纤维细胞。基因组序列分析表明，患者携带c.1621A>C和c.591_594del的复合杂合突变，导致p.S541R和p.Y197* inERCC 2：然后，患者被诊断为XP-D。Y197* 以前没有被描述过。结论她的轻度皮肤表现可能归因于她的基因组上的突变位点和日常严格的防晒。c.1621A>C可能是日本XP‐D患者中ERCC 2的创始突变，因为它在日本XP‐D患者中最常见，并且在日本以外的其他地方尚未发现。
BackgroundMost patients with xeroderma pigmentosum complementation group D (XP‐D) from Western countries suffer from neurological symptoms, whereas Japanese patients display only skin manifestations without neurological symptoms. We have previously suggested that these differences in clinical manifestations in XP‐D patients are attributed partly to a predominant mutation inERCC2, and the allele frequency of S541R is highest in Japan.MethodsWe diagnosed a child with mild case of XP‐D by the evaluation of DNA repair activity and whole‐genome sequencing, and followed her ten years.ResultsSkin cancer, mental retardation, and neurological symptoms were not observed. Her minimal erythema dose was 41 mJ/cm2, which was slightly lower than that of healthy Japanese volunteers. The patient's cells showed sixfold hypersensitivity to UV in comparison with normal cells. Post‐UV unscheduled DNA synthesis was 20.4%, and post‐UV recovery of RNA synthesis was 58% of non‐irradiated samples, which was lower than that of normal fibroblasts. Genome sequence analysis indicated that the patient harbored a compound heterozygous mutation of c.1621A>C and c.591_594del, resulting in p.S541R and p.Y197* inERCC2: then, patient was diagnosed with XP‐D. Y197* has not been described before.ConclusionHer mild skin manifestations might be attributed to the mutational site on her genome and daily strict sun protection. c.1621A>C might be a founder mutation ofERCC2among Japanese XP‐D patients, as it was identified most frequently in Japanese XP‐D patients and it has not been found elsewhere outside Japan.