1个表皮松解性掌跖角化症家系角蛋白9基因检测及产前诊断

Genetic analysis and prenatal diagnosis of keratin 9 gene in a pedigree with epidermolytic palmoplantar keratoderma

目的分析1个表皮松解性掌跖角化症(epidermolytic palmoplantar keratoderma,EPPK)家系角蛋白9(keratin 9,KRT9)基因突变情况,并进行产前诊断.方法收集EPPK家系6例患者及家系所有表型正常成员外周血,提取DNA,采用PCR扩增KRT9基因第1~7外显子,并采用Sanger法进行基因测序检测KRT9基因突变.明确KRT9基因突变后,采集先证者羊水进行产前诊断并随访.结果 6例患者均检测到KRT9基因第1外显子存在c.487C>T(p.R163W)杂合突变,该突变可导致其编码的第163位精氨酸被色氨酸代替(p.R163W),家系中表型正常成员该位点均无突变;先证者羊水产前诊断结果示胎儿未携带致病突变c.487C>T,新生儿出生后随访12个月,未见EPPK表型.结论 KRT9基因c.487C>T(p.R163W)杂合突变是该EPPK家系的致病机制,基因诊断和产前诊断可有效降低生育患病儿的风险.

Objective To identify the mutation of keratin 9(KRT9) in a pedigree with epidermolytic palmoplantar keratoderma(EPPK) for prenatal diagnosis. Methods Peripheral blood sample of 6 EPPK patients and all family members with normal phenotype were collected for extraction of DNA. The exon 17 of KRT9 gene was amplified by PCR and the mutation of KRT9 gene was detected by Sanger sequencing. The amniotic fluid samples of the proband were collected for prenatal diagnosis after the verification of KRT9 gene mutation. Results A heterozygous mutation of c.487 C>T(p.R163 W) was detected in exon 1 of KRT9 gene in these 6 EPPK patients resulting in the substitution of arginine at position 163 by tryptophan(p.R163 W), and it was not detected in the family members with normal phenotype. Prenatal diagnosis of fetal amniotic fluid showed no pathogenic mutation of c.487 C > T. No EPPK phenotype was found in the newborn after 12-month follow-up. Conclusion The heterozygous mutation of c.487 C>T(p.R163 W) in KRT9 gene is the cause of EPPK. Gene diagnosis and prenatal diagnosis can effectively prevent the risk for EPPK newborn.