Carvajal综合征一例伴桥粒斑蛋白基因新突变

【摘要】 目的 对1例临床表现为羊毛状发，膝盖、掌跖角化性皮损，暂无心脏症状的患儿进行基因突变检测。方法 收集患儿及其父母的临床资料。提取患儿、其父母及100例无关健康对照者外周血DNA，采用二代皮肤靶向测序包检测患儿的基因突变，应用Sanger测序法进行验证。结果 患儿女，3岁，出生头发卷曲，8月龄出现掌跖角化并渐累及膝盖，其父母表型正常。测序发现，患儿桥粒斑蛋白（DSP）基因第23号外显子存在移码突变c.5152dupT（p.L1718Ffs*15），DSP基因第24号外显子检测到无义突变c.C6478T（p.R2160X）。其母亲DSP基因第23号外显子亦存在c.5152dupT移码突变，但第24号外显子未检测到相关突变。其父亲及100例健康对照中均未检测到相关突变。诊断：Carvajal综合征。结论 该例Carvajal综合征患儿存在DSP基因复合杂合突变c.5152dupT（p.L1718Ffs*15）和c.C6478T（p.R2160X），可能与其发病有关。

Novel desmoplakin mutations in a child with Carvajal syndrome

Objective To detect genetic mutations in a child with woolly hair and keratotic skin lesions on the knees,palms and soles but without cardiac symptoms.Methods Clinical data were collected from the patient and her parents,and DNA was extracted from peripheral blood of the patient,her parents and 100 unrelated healthy controls.A next-generation skin-targeted sequencing panel was used to detect gene mutations,and Sanger sequencing was performed for verification.Results The 3-year-old female patient had presented with curly hair since birth,palmoplantar keratoderma with knee involvement since the age of 8 months.Phenotypes of the patient′s parents were normal.Sequencing revealed a frameshift mutation c.5152dupT(p.L1718Ffs*15)in exon 23 and a nonsense mutation c.C6478T(p.R2160X)in exon 24 of the desmoplakin(DSP)gene in the patient.The frameshift mutation c.5152dupT was also identified in her mother,but no mutation was found in exon 24 of the DSP gene in her mother.No mutation was found in the patient′s father or the 100 healthy controls.The patient was diagnosed with Carvajal syndrome.Conclusion Compound heterozygous mutations in the DSP gene were identified in the patient with Carvajal syndrome,including c.5152dupT(p.L1718Ffs*15)and c.C6478T(p.R2160X)mutations,which may contribute to the occurrence of Carvajal syndrome.