Human Genome Laboratory, Department for Molecular and Developmental Genetics, VIB, 3000 Leuven, Belgium.
Clin Genet. 2009 Dec;76(6):535-43. doi: 10.1111/j.1399-0004.2009.01248.x. Epub 2009 Oct 23.
Focal dermal hypoplasia (FDH), Goltz or Goltz-Gorlin syndrome, is an X-linked dominant multisystem disorder characterized primarily by involvement of the skin, skeletal system and eyes. We screened for mutations in the PORCN gene in eight patients of Belgian and Finnish origin with firm clinical suspicion of FDH. First, we performed quantitative PCR (qPCR) analysis to define the copy number at this locus. Next, we sequenced the coding regions and flanking intronic sequences of the PORCN gene. Three de novo mutations were identified in our patients with FDH: a 150-kb deletion removing six genes including PORCN, as defined by qPCR and X-array-CGH, and two heterozygous missense mutations; c.992T>G (p.L331R) in exon 11 and c.1094G>A (p.R365Q) in exon 13 of the gene. Both point mutations changed highly conserved amino acids and were not found in 300 control X chromosomes. The three patients in whom mutations were identified all present with characteristic dermal findings together with limb manifestations, which were not seen in our mutation-negative patients. The clinical characteristics of our patients with PORCN mutations were compared with the previously reported mutation-positive cases. In this report, we summarize the literature on PORCN mutations and associated phenotypes.
局限性皮肤发育不良（FDH），又称 Goltz 或 Goltz-Gorlin 综合征，是一种 X 连锁显性多系统疾病，主要表现为皮肤、骨骼系统和眼睛受累。我们对 8 名具有明确 FDH 临床疑似症状的比利时和芬兰血统患者进行了 PORCN 基因突变筛查。首先，我们进行了定量 PCR（qPCR）分析，以确定该基因座的拷贝数。接下来，我们对 PORCN 基因的编码区和侧翼内含子序列进行了测序。我们在 FDH 患者中发现了 3 个新生突变：qPCR 和 X 染色体微阵列比较基因组杂交（X-array-CGH）定义的 150kb 缺失，导致包括 PORCN 在内的 6 个基因缺失，以及两个杂合错义突变；c.992T>G（p.L331R）位于 11 号外显子，c.1094G>A（p.R365Q）位于 13 号外显子。这两个点突变改变了高度保守的氨基酸，在 300 个对照 X 染色体中未发现。在确定突变的 3 名患者中，均存在特征性的皮肤表现和肢体表现，而我们的突变阴性患者则没有这些表现。我们将具有 PORCN 基因突变的患者的临床特征与先前报道的突变阳性病例进行了比较。在本报告中，我们总结了 PORCN 基因突变及其相关表型的文献。
