摘要
目的探讨1例Netherton综合征(NS)早产儿的临床表型及遗传学特点。方法选取2020年3月浙江大学医学院附属儿童医院确诊的1例SPINK5基因变异所致的NS患儿为研究对象。收集患儿的临床资料及家族史。采集患儿及其父母的外周静脉血样各2 mL, 提取基因组DNA, 进行全外显子组测序(WES), 用Sanger测序法对候选变异进行验证。根据美国医学遗传学与基因组学学会(ACMG)相关指南对候选变异进行致病性评级和有害性分析。本研究通过了浙江大学医学院附属儿童医院伦理委员会的审查(批准号:2024-IRB-0251-P-01)。结果患儿为女性, 出生2天, 35^(+3)孕周因"胎膜早破4^(+)小时"出生, 生后即发现全身皮肤剥脱, 羊水呈豆腐渣样。经抗感染、保湿治疗后好转, 之后仍有周期性脱皮。家族中无类似病例。WES检测显示患儿携带SPINK5基因第14外显子c.1130delG(p.G377Efs*127)杂合变异(母源性)以及第1 ~ 33外显子缺失(父源性)。结论本例NS为早产儿, 宫内发病, 既往未见报道。c.1130delG(p.G377Efs*127)变异的检出丰富了SPINK5基因的变异谱。
Objective To explore the clinical characteristics and genetic variant in a premature infant with Netherton syndrome(NS).Methods A neonate with NS caused by variants of SPINK5 gene diagnosed at the Children's Hospital Affiliated to Zhejiang University School of Medicine in March 2020 was selected as the study subject.Clinical data and family history were collected.Peripheral blood samples(2 mL each)were obtained from the child and her parents for whole-exome sequencing(WES).Candidate variants were subjected to pathogenicity classification and deleteriousness evaluation.This study has been approved by the Medical Ethics Committee of the Hospital(Ethics No.2024-IRB-0251-P-01).Results The infant was born prematurely at 35^(+3) weeks due to“premature rupture of membranes for 4 hours"”and exhibited generalized skin peeling,with meconium-stained amniotic fluid resembling bean curd residue.The condition improved with supportive treatments such as anti-infection and moisturizing therapy,though periodic hair loss had persisted.No similar case was reported by family history.WES has revealed a heterozygous c.1130delG(p.G377Efs*127)variant in exon 14 of the SPINK5 gene,which was inherited from her mother,and deletion of exons 1~33 of the SPINK5 gene,which was inherited from her father.Conclusion This case of NS presented with intrauterine onset in a preterm infant,which has not been previously reported.The identification of c.1130delG(p.G377Efs*127)variant has expanded the mutation spectrumof the SPINK5 gene.
作者
胡玲玲
詹灿阳
韩铭玉
袁天明
陈理华
Hu Lingling;Zhan Canyang;Han Mingyu;Yuan Tianming;Chen Lihua(Department of Neonatology,Children's Hospital Affiliated to Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou,Zhejiang 310052,China)
出处
《中华医学遗传学杂志》
2025年第3期330-335,共6页
Chinese Journal of Medical Genetics
