新生儿Goltz综合征PORCN基因新发突变一例

A de novo mutation in the PORCN gene in a newborn with Goltz syndrome

目的报道1例新生儿Goltz综合征及PORCN基因新发突变位点。方法回顾性分析1例Goltz综合征新生儿的临床资料,采集患儿及父母外周静脉血,提取基因组DNA,全外显子组测序筛查患儿致病基因,Sanger测序法验证突变基因。结果患儿女,出生后7 h因头皮缺损、面部、双膝关节内侧多发表皮缺损、左耳廓畸形、右手中指无名指并指、右足拇指二趾并趾、左足呈“龙虾爪”畸形就诊。基因检测显示,患儿PORCN基因第4外显子第514~521位插入了一段重复的TCCTTCCA片段(c.514_521dupTCCTTCCA),导致第175号氨基酸由丝氨酸变为脯氨酸(p.S175Pfs*14),并引起该蛋白的翻译在此后第14个密码子终止。患儿父母均未检测到此杂合突变。该患儿确诊为Goltz综合征。结论Goltz综合征有多种表型,结合PORCN基因突变可确诊。c.514_521dupTCCTTCCA杂合突变为新突变。

Objective To report a newborn with Goltz syndrome and a de novo mutation in the PORCN gene.Methods Clinical data collected from the newborn with Goltz syndrome were retrospectively analyzed.Peripheral venous blood samples were obtained from a newborn and her parents,genomic DNA was extracted,whole-exome sequencing was performed to screen disease-causing genes in the patient,and Sanger sequencing was conducted to verify the mutant genes.Results The 7-hour-old female newborn presented with scalp defects,multiple epidermal defects on the face,inner sides of both knee joints,deformity of the left auricle,syndactyly of the middle and ring fingers of the right hand as well as the great and second toes of the right foot,and lobster-claw deformity of the left foot.Genetic testing showed that a fragment TCCTTCCA was inserted at position 514-521 in exon 4 of the PORCN gene of the patient(c.514_521dupTCCTTCCA),resulting in the substitution of serine by proline at amino acid position 175(p.S175Pfs*14),followed by the translation termination at the 14th codon.This heterozygous mutation was not found in his parents.The patient was diagnosed with Goltz syndrome.Conclusion There are various phenotypes of Goltz syndrome,and a confirmed diagnosis of Goltz syndrome can be made based on PORCN gene mutations and clinical manifestations.The heterozygous mutation c.514_521dupTCCTTCCA is a novel mutation.