局灶性真皮发育不全患者PORCN基因突变研究

A novel PORCN gene mutation in a patient with focal dermal hypoplasia

目的 检测局灶性真皮发育不全（focal dermal hypoplasia,FDH）患者PORCN基因突变情况,探讨基因型与表型的相关性.方法 收集1例局灶性真皮发育不全患者及其家系3名正常成员及50名无血缘关系的健康对照者的外周血,采用PCR扩增PORCN基因所有外显子及其邻近的剪切位点进行直接测序.结果 患者PORCN基因核苷酸序列第2外显子上第149位碱基由G变为C,导致第38位氨基酸丙氨酸被脯氨酸代替（A38P）,该患者家属及健康对照无此突变.患者临床表现中度.结论 该患者存在PORCN基因A38P突变,为一新的错义突变,可能是导致FDH发病机制之一.G149C基因型与中度的表型之间的关系与A38P错义突变对蛋白的影响有关,与以往结论不同.

Objective To detect the mutation of PORCN gene in a patient with focal dermal hypoplasia and study the genotype-phenotype correlation. Methods Peripheral blood samples were obtained from the family members and control subjects. PCR was carried out to amplify all the exons and adjacent splice sites of PORCN gene and mutation was detected by bidirectional sequencing. Results A G149C mutation was found at exon 2 of the PORCN gene in the patient, which caused a change from Alanine to Proline at eodon 38 （A38P）. The patient presented mild clinical manifestations. Conclusion A new missense mutation （A38P） in the PORCN was detected in the patient, which maybe one of the molecular mechanisms in the pathogenesis of the disease. The relationship between G149C genotype and moderate phenotype might be attributed to the influence of A38P missense mutation towards the corresponding protein, which is different from previous results.