摘要目的 报道1例桥粒斑蛋白(DSP)基因自发突变导致的Carvajal综合征.方法 在郑州大学第一附属医院皮肤科收集1例Carvajal综合征患者临床资料.抽取先证者及其父母和100例无关健康人外周血,提取血液基因组DNA,应用Ion torrent PGM二代测序平台检测先证者家系皮肤病相关基因各外显子编码区域的序列突变情况,PCR-Sanger测序验证致病性突变.结果 先证者临床表现为羊毛状发,弥漫性掌跖角化,甲发育不良,牙齿发育不良,心电图示窦性心律不齐.基因测序显示,先证者DSP基因第14外显子发生杂合错义突变c.1790C＞T(p.Ser597Leu),导致其编码蛋白质第597位丝氨酸突变为亮氨酸.先证者父母及100例健康对照均未发现该位点突变,先证者为自发突变.依据患者临床表现、基因检测及辅助检查结果,最终诊断Carvajal综合征.结论 DSP基因杂合突变c.1790C＞T(p.Ser597Leu)可能是引起该患者临床表型的致病突变.

abstractsObjective To report a case of Carvajai syndrome caused by a spontaneous mutation in the desmoplakin (DSP) gene.Methods Clinical data were collected form a patient with Carvajal syndrome in Department of Dermatology,The First Affiliated Hospital of Zhengzhou University.Peripheral blood samples were obtained from the proband,his parents and 100 unrelated healthy controls,and blood genomic DNA was extracted.The ion torrent PGM second-generation sequencing platform was used to detect sequence variations in coding regions of exons in skin disease-related genes in the proband and his parents,and the pathogenic variation was verified by PCR-Sanger sequencing.Results The proband clinically presented with woolly hair,diffuse palmoplantar keratoderma,onychodysplasia,hypodontia and sinus arrhythmia as shown by electrocardiogram.Gene sequencing revealed a heterozygous missense mutation c.1790C＞T (p.Ser597Leu) in exon 14 of the DSP gene in the proband,resulting in the substitution of serine by leucine at amino acid position 597.No mutation was identified in the proband's parents or the 100 healthy controls,so the mutation in the proband is spontaneous.The patient was finally diagnosed with Carvajal syndrome according to the clinical manifestations,gene detection and auxiliary examination results.Conclusion The heterozygous missense mutation C.1790C＞T (p.Ser597Leu) of the DSP gene may be the pathogenic mutation for the clinical phenotype of the patient.