不伴套叠性脆发的2例Netherton综合征致病基因突变检测

Genetic diagnosis of two Netherton syndrome patients without bamboo hair

目的:通过基因检测的方法,确诊2例不伴有套叠性脆发表现的Netherton综合征患者。方法:采集患者临床资料,进行皮损组织病理检查及毛发镜检,提取患者及其相关亲属外周血DNA,采用PCR扩增相应可疑致病基因编码区的全部外显子及其侧翼序列并测序。结果:2例患者毛发均未见明显形态学异常。基因检测发现例1及其受累的妹妹SPINK5基因发生c.2260A>T纯合突变,导致氨基酸出现p.Lys754*改变,未受累的父母及兄长为该突变的杂合携带者;例2的SPINK5基因发生c.1432C>T及c.1693-2del A复合杂合突变,导致氨基酸出现p.Gln478*及剪切位点改变,突变分别来自其健康父母。200例健康正常对照者均未见相同突变。患者CDSN、KRT1、KRT10、KRT2及DSG1基因均未见致病性突变。结论:通过基因检测确诊2例Netherton综合征患者,基因检测为确诊临床表现不典型Netherton综合征的重要方法。

Objective： To diagnose atypical Netherton syndrome without bamboo hair （trichorrhexis invaginata）, using genetic approaches. Methods： In addition to the collection of patients＇clinical data, scalp and eyebrow hair were examined with a mi- croscopy. Blood samples from the patients and their immediate relatives were used for gene analysis. All the coding exons along with the flanking sequences of the suspected genes （SPINKS, CDSN, KRT1, KRT2, KRT10 and DSG1） were amplified by PCR and sequenced. Results： Although no abnormalities were found in either patient＇s hair, patient #1 and his affected sister showed a homozygous missense mutation （e.2260A〉T） in the SPINK5 gene, leading to an alteration of p.Lys754＊. Patient #1 ＇s uninvolved parents and siblings were carriers of a heterozygous mutation. Meanwhile patient #2 showed compound heterozygous mutations （e. 1432C〉T and c.1693-2delA）, leading to a p.Gln478＊ alteration and aberrant mRNA splicing. Patient #2＇s parents were heterozy- gous carriers of the corresponding mutations. None of the mutations were detected in 200 ethnically matched normal controls. Both patients had no gene mutations in CDSN, KRT1, KRT2, KRT10 or DSG1. Conclusion： We confirm two cases of Netherton syndrome by genetic approaches. Genetic analysis could be critical in the diagnosis of atypical Netherton syndrome.