色素失禁症1家系NEMO基因新致病突变报道

【摘要】 目的 对1个色素失禁症家系进行基因诊断，以明确致病基因突变位点。方法 收集整理该家系所有患者的临床资料。提取该家系中患者、健康人、100例无关健康对照外周静脉血细胞DNA，针对NEMO基因外显子区及其侧翼序列进行Sanger测序。结果 该家系4代共4例患者，均有典型皮损，其他症状各有差异。基因测序示先证者及其他3例患者均存在NEMO基因8号外显子的杂合无义突变c.1153C>T（p.Gln385X），编码区第1153位碱基由C突变为T，导致肽链第385位谷氨酰胺密码子（CAG）变成终止密码子（TAG）,14例健康亲属和100例健康对照未发现该突变。该突变与色素失禁症符合共分离，数据库查询显示其为新发无义突变，美国遗传学与基因组学学会指南判定致病证据为极强致病位点。结论 NEMO基因突变c.1153C>T与该家系色素失禁症发病有关。

A novel pathogenic mutation in the NEMO gene in a family with incontinentia pigmenti

【Abstract】 Objective To identify gene mutations in a family with incontinentia pigmenti, in order to confirm pathogenic mutations. Methods Clinical data were collected from all patients in a family with incontinentia pigmenti. DNA was extracted from peripheral blood samples obtained from the patients, healthy members in the family, and 100 unrelated healthy controls, and Sanger sequencing was performed for all exons and their flanking sequences of the NEMO gene. Results Totally, there were 4 patients in the 4-generation family, who all presented with typical skin lesions and different symptoms. Genetic testing indicated that the proband and the other 3 patients all carried a heterozygous nonsense mutation c.1153C>T （p.Gln385X） at position 1153 in exon 8 of the NEMO gene, which led to the substitution of the glutamine codon （CAG） by the termination codon （TAG） at amino acid position 385. The mutation was not identified in the 14 healthy relatives or 100 unrelated healthy controls. The mutation cosegregated with incontinentia pigmenti in the family. Database searching confirmed the mutation to be a novel nonsense mutation, and it was considered as a very strong pathogenic locus according to the American College of Medical Genetic and Genomics guidelines. Conclusion The mutation c.1153C>T in the NEMO gene is associated with the occurrence of incontinentia pigmenti in this family.