色素失禁症临床表型与NEMO基因突变7例并文献复习

目的:探讨色素失禁症（IP）在中国儿童的临床表型及NEMO基因突变特点。方法:分析2009至2012年复旦大学附属儿科医院（我院）收治的7例IP患儿临床表型和NEMO基因突变，检索PubMed、Web of Science、中国知网、维普中文科技期刊数据库及中国生物医学文献数据库，检索研究对象为中国人的IP文献，汇总中国IP患儿临床表型和NEMO基因的突变数据。结果:我院7例IP患儿临床表型除有典型的皮肤损害外，主要还有神经系统和眼部受累，5例NEMO基因共有序列NEMO△4-10缺失，2例外显子测序，未发现致病性突变位点，其中1例发现1个纯合SNP。汇总我院7例和文献检索到的69例中国IP患儿（76例）数据显示，女68例，男8例；92.1%（70例）在新生儿期发病，21.1%（16例）有阳性家族史；均有皮肤受累，53.9%（41/76）神经系统受累，24.2%（16/66）眼部受累，39.6%（19/48）牙齿受累，31.0%（22/71）毛发受损，7.9%死亡（6/76），其他少见临床表型：先天性心脏病3例，骨骼发育缺陷、环状胰腺和肺囊变各1例；58.3％（21/36）血嗜酸性粒细胞升高；皮肤组织活检阳性率达95.7%（22/23）。48/76例行基因检测的IP患儿中，30/48例（62.5％）发现有NEMO基因突变，其中大片段缺失27例（假基因缺失3例），点突变2例和单个碱基缺失1例。结论:中国IP患儿散发病例占多数，绝大多数在新生儿期即发现典型的皮肤损害，其次为神经系统、牙齿受累和眼部受累。皮肤病理活检阳性率非常高。NEMO基因的突变检出率为62.5%，可对患儿进行合理的产前诊断和早期干预。

NEMO gene mutations and clinical manifestations in 7 neonatal patients with incontinentia pigmenti and literature review

Objective Incontinentia pigmenti （IP） is a rare X-linked dominant disorder that affects ectodermal tissues. This study aims to analyze the NEMO mutation and clinical features of Chinese IP cases. Methods NEMO mutation and clinical features of seven IP inpatients from 2009 to 2012 of our hospital were analyzed. A literature search was performed using the search strategy of ＂Incontinentia Pigmenti＂ AND chinese among PubMed, Web of Science, CNKI, VIP from establishment of the database till now. Data of clinical features and NEMO mutation of Chinese IP cases were analyzed. Results Seven IP cases from our hospital manifested classic cutaneous features and neurological and ocular manifestations were also detected. The NEMOz~4-10 deletion of the NEMO gene was detected in 5 （71.4%） of 7 patients. In 2 patients without NEMOA4-10 deletion pathogenic mutations were not found in 10 exons, only a homozygous SNP was found in one patient. 76 IP patients including 68 females and 8 males had cutaneous manifestations （100%） , 70 cases （92.1%） were found clinical manifestions in neonatal period. 16 cases（24.2% ） had family history, 41 cases （ 53. 9% ） with combination of nerve system abnormalities, 16/66 cases （ 24. 2% ） with ocular manifestations, dental manifestations were observed in 19/48 cases （39.6%）, hair abnormalities were found in 22/71 cases （31.0%） , and 6 cases died （7.9%）. Other manifcstions included congenital heart disease, skeletal dyspalsia, annular pancreas and pulmonary cystic. A higher blood eosinophilia was observed in 58.3% IP cases. The positive rate of skin biopsy was 95.7%. 30 IP cases were detected with NEMO mutation （62.5%）, 27 cases with NEMOA4-10 deletion, 3 cases were detected with pseudogene NEMO exon 4-10 deletion in those patients. Two cases were detected with point mutation and 1 case had single nucleotide deletion. Conclusions Chinese 1P cases were mostly sporadic. Almost all patients were found with typical cutaneous manifestations at birth or shortly after birth. In addition to cutaneous manifestations, neurological and ocular manifestations are also detected. The positive rate of skin biopsy in China was as high as 95.7%, which is helpful to diagnosis. NEMO gene mutation detection ratio in China is about 62.5% , gene diagnosis and prenatal diagnosis may be reasonable for treatment and prognosis, andprovide appropriate genetic counseling for family.