Fernandes Priscilla H, Wen Shu, Sutton Vernon Reid, Ward Patricia A, Van den Veyver Ignatia B, Fang Ping
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Genet Test Mol Biomarkers. 2010 Oct;14(5):709-13. doi: 10.1089/gtmb.2010.0089. Epub 2010 Sep 20.
Focal dermal hypoplasia (FDH) is an X-linked dominant disorder caused by mutations in the gene PORCN, which encodes a protein required for the secretion and signaling of Wnt proteins. While deletions are responsible for a small percentage of FDH-causing mutations, the vast majority of mutations are single-nucleotide substitutions or small deletions or insertions that can be identified by sequence analysis. In 2007, we implemented a PORCN gene sequencing test for individuals with a clinical diagnosis of FDH. To date, we have detected 12 novel PORCN mutations and 6 previously reported mutations in 53 such unrelated patients. The pathogenic PORCN mutations included nine nonsense mutations, three missense mutations, one small deletion, two small duplications, and three splice-site mutations. Of these mutations, two were found in affected men and were mosaic; one of these was found in three other affected women. The remaining 16 mutations were found only in women. All the mutations detected in women were presumed heterozygous. In addition to the disease-causing mutations, eight nucleotide variants of unknown significance were identified. Further characterization of these variants suggests that four of them are pathogenic mutations. These findings add to the heterogeneity of mutations in the PORCN gene that cause FDH.
局灶性真皮发育不全（FDH）是一种X连锁显性疾病，由PORCN基因突变引起，该基因编码Wnt蛋白分泌和信号传导所需的一种蛋白质。虽然缺失导致的FDH致病突变占比小，但绝大多数突变是单核苷酸替换或小的缺失或插入，可通过序列分析鉴定。2007年，我们对临床诊断为FDH的个体开展了PORCN基因测序检测。迄今为止，我们在53例此类无血缘关系的患者中检测到12种新的PORCN突变和6种先前报道的突变。致病性PORCN突变包括9种无义突变、3种错义突变、1种小缺失、2种小重复和3种剪接位点突变。在这些突变中，2种在患病男性中发现且为嵌合体；其中1种在另外3名患病女性中发现。其余16种突变仅在女性中发现。在女性中检测到的所有突变均假定为杂合子。除致病突变外，还鉴定出8种意义不明的核苷酸变异。对这些变异的进一步表征表明，其中4种是致病突变。这些发现增加了导致FDH的PORCN基因突变的异质性。
