SERPINB7基因突变长岛型掌跖角化病一家系3例临床研究

Clinical analysis of 3 cases of SERPINB7 gene mutation in Nagashima-type palmoplantar keratosis family

目的总结一家系3例SERPINB7基因突变长岛型掌跖角化病患者及先证者父母SERPINB7基因突变情况。方法采集该家系3例掌跖角化病患者(先证者及其姐姐、叔叔)及先证者父母的外周血,提取基因组DNA,采用高通量测序法检测皮肤病相关基因各外显子编码区域的序列变异情况,对致病性变异经PCR-Sanger测序验证,并与100例健康者进行比较。结果先证者及其姐姐、叔叔临床表现为双手掌、双足足底红斑基础上角化过度。基因测序显示,先证者及其姐姐、叔叔SERPINB7基因携带c.336+2T>G和c.522dupT位点复合杂合突变,先证者父亲携带c.522dupT(p.V175Cfs*45)杂合移码突变,先证者母亲携带c.336+2T>G(splicing)杂合剪切突变;100例健康对照均未见c.336+2T>G(splicing)杂合剪切突变和c.522dupT位点杂合移码突变。结论 SERPINB7基因c.336+2T>G和c.522dupT位点的复合杂合突变可能是该家系3例长岛型掌跖角化病患者的致病原因。

Objective To analyze the clinical data of SERPINB7 gene mutations in 3 patients with Nagashima-type palmoplantar keratosis and the parents of the proband. Methods Three cases of palmoplantar keratosis(the proband and his sister and uncle) and the parents of the proband were collected peripheral blood to extract genomic DNA. High-throughput sequencing was used to detect the exon codes of skin disease-related genes. The sequence variation of the region was verified by PCR-Sanger sequencing for pathogenic variation, and compared with 100 healthy controls. Results The proband and his sister and uncle were clinically manifested by hyperkeratosis based on the palms of both hands and the soles of the feet. The gene sequencing showed that the proband and his sister and uncle carried c.336+2 T>G and c.522 dupT. The proband’s father carried c.522 dupT(p.V175 Cfs * 45) heterozygous frameshift mutation, and the proband’s mother carried c.336+2 T>G(splicing) heterozygous splicing mutation. Neither c.336+2 T>G(splicing) heterozygous splicing mutations nor c.522 dupT site heterozygous frameshift mutations was found in 100 healthy controls. Conclusion The compound heterozygous mutations of c.336+2 T>G and c.522 dupT locus in SERPIB7 gene might be the cause of 3 cases of Nagashima-type palmoplantar keratosis in this family.