论文部分内容阅读
目的:总结报道中国第2例DeSanto-Shinawi脑病(DESSH)患儿的临床特点和致病的n WAC基因突变谱。n 方法:采用回顾性分析对1例先后在湖北医药学院附属襄阳市第一人民医院和武汉科技大学附属天佑医院就诊和定期随访的DESSH患儿进行临床特征和生长发育评估，分析所有n WAC突变所致DESSH的临床表型与基因突变谱关系。n 结果:患儿，女，定期随访至1岁3个月，生长发育、智能发育迟缓，四肢肌张力减低，面容特殊，头小。全外显子测序发现一种新发n WAC基因致病突变(c.1090dupA，p.Arg364Lysfs*14)。纳入已报道的29个家系31例DESSH患者进行分析，发现导致DESSH发病的n WAC基因突变均为无义突变或移码突变，25例(88.6%)为n WAC基因新发突变，6例(19.4%)为生殖腺嵌合遗传。所有突变均导致位于WAC蛋白C末端的卷曲螺旋区(CC)缺失，仅35.5%的患者同时有WW结构域缺失。n 结论:本例为新发n WAC基因移码突变引起，患儿发病较早且较严重。DESSH以特殊面容、全面发育落后和癫痫性脑病为特点，n WAC基因导致WAC蛋白的CC缺失是致病关键，基因型与表现型间缺乏明确对应关系。n “,”Objective:To report the second Chinese DeSanto-Shinawi syndrome (DESSH) case and to summarize the clinical characteristics and n WAC gene mutation profiling in all published cases.n Methods:A retrospective analysis was performed to evaluate the clinical characteristics and growth and development of a child with DESSH who had been regularly followed up in the Xiangyang No. 1 People′s Hospital, Hubei Medical College and Tianyou Hospital Affiliated to Wuhan University of Science and Technology.The relevant literature was reviewed to assess the relationship between clinical phenotype and spectrum of n WAC gene mutation.n Results:The female baby with DESSH was regularly evaluated for growth and development till the present age of 1 year and 3 months.She presented with growth and mental retardation, hypotonia, facial dysmophism and microcephaly.Whole-exome sequencing revealed a new de novo pathogenic mutation in the n WAC gene (c.1090dupA, p.Arg364Lysfs*14) that has not been reported before.Analysis of 31 reported DESSH cases from 29 families showed that all of them had nonsense mutations or frame-shift mutations in n WAC gene, which resulted in the loss of the coiled-coil region of WAC.Twenty-five cases (88.6%) were new mutations of WAC, and 6 cases (19.4%) were chimeric inheritance of gonad.Only 35.5% of them simultaneously lost both the WW domain in truncated WAC protein.n Conclusions:DESSH is characterized by facial dysmophism, overall developmental delay and epileptic encephalopathy.This second Chinese DESSH baby was severe with an earlier onset and caused by a new mutation in n WAC gene.All DESSH is caused by nonsense mutations or frameshift mutations of n WAC gene resulting in the loss of coiled-coil region.There is no significant corresponding phenotype-genotype correlations in those DESSH cases.n