色素失禁症NEMOΔ4～10基因片段缺失的初步研究

目的 了解我国色素失禁症病例的NEMO基因共有序列NEMOΔ4～10缺失情况。方法 儿童色素失禁症病例7例及其部分家庭成员共15人被纳入实验组,同期50例无血缘关系,无遗传性疾病儿童随机抽取作为正常对照。依据色素失禁症基因结构特点,选取NEMO基因特异引物In2／JF3R和假基因ΔNEMO特异引物Rev-2／JF3R,采用长链聚合酶链反应(PCR)进行检测。结果 7例患儿5例(5／7)(例1、2、3、4和6)有NEMO基因共有序列NEMOΔ4～10缺失,其中例1和例6母女患病,母亲1a和6a检测结果同样显示有NEMO基因共有序列NEMOΔ4～10缺失;7例患儿,只有例2和例4假基因ANEMO中出现共有序列NEMOΔ4～10缺失,相关家族成员假基因ANEMO无共有序列NEMOΔ4～10缺失。正常对照组50例NEMO和假基因ANEMO均未发现有共有序列NEMOΔ4～10缺失。结论 色素失禁症基因突变方式大部分为NEMO基因共有序列NEMOΔ4～10缺失。

NEMO Delta 4-10 deletion of NEMO gene in Chinese incontinentia pigmenti cases

OBJECTIVE: Incontinentia pigmenti (IP) is a rare X-linked dominant disorder that affects ectodermal tissues. In IP, mutations in NEMO lead to the complete loss of NF-kB activation creating a susceptibility to cellular apoptosis in response to TNF-alpha. Recently, a second nonfunctional copy of the gene, Delta NEMO was identified, opposite in direction to NEMO. Almost 90% of IP whose gene mutation type had been recognized have a recurrent genomic deletion of exons 4-10 of the NEMO (IKK gamma) gene, called NEMO Delta 4-10, which is necessary to activate the NF-kB pathway. Therefore, PCR-based detection of the NEMO deletion is a diagnostic measurement for IP. This study sought to analyze the NEMO Delta 4-10 deletion in NEMO gene of Chinese IP cases. METHODS: Seven IP cases and part of their families totally 15 persons were enrolled in this study. The 7 IP cases were aged 41 days to 8 years. Among them 1 was male and 6 were female. Four cases had family history of IP, the other 3 were sporadic cases. Fifty healthy children without any congenital diseases were taken as normal control group. According to the gene characteristics of IP, by PCR measurement NEMO Delta 4-10 deletion in NEMO gene was tested with specific primers In2/JF3R, and NEMO Delta 4-10 deletion in pseudogene Delta NEMO was checked out by primers Rev-2/JF3R. RESULTS: Five out of the 7 tested cases (case 1, 2, 3, 4, and 6) showed NEMO Delta 4-10 deletion in NEMO gene. The mothers of case 1 and case 6, 1a and 6a, also suffered from this disease, and their results were just the same as their daughters. For pseudogene Delta NEMO only case 2 and case 4 were proved having NEMO Delta 4-10 deletion, while other cases and families had negative results. For normal control group, NEMO Delta 4-10 deletion was not found either in NEMO gene or in their pseudogene Delta NEMO. CONCLUSION: Incontinentia pigmenti in most cases were caused by NEMO Delta 4-10 deletion in NEMO gene.