Phenotype and genotype in 17 patients with Goltz-Gorlin syndrome
Phenotype and genotype in 17 patients with Goltz-Gorlin syndrome
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DOI：
10.1136/jmg.2009.068403
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发表时间：
2009-10-01
影响因子：
4
通讯作者：
Hennekam, Raoul C. M.
中科院分区：
文献类型：
--
作者：
Maas, S. M.;Lombardi, M. P.;Hennekam, Raoul C. M.
背景资料：Goltz-Gorlin综合征或局灶性皮肤发育不全是一种高度可变的X连锁显性综合征，伴有外胚层和中胚层起源的异常。2007年，发现PORCN基因突变是Goltz-Gorlin综合征的病因。方法：报告了一系列17例Goltz-Gorlin综合征患者，并描述了他们的表型和基因型。结果：14例13名女性和1名男性患者中，发现PORCN突变。突变包括无义（n = 5），移码（n = 2），异常剪接（n = 2）和错义（n = 5）突变。没有发现基因型-表型相关性，所有具有典型综合征特征的患者都有可检测到的突变。在3例女性非典型体征中，未发现突变，1例男性患者具有典型特征，成纤维细胞中显示PORCN无义突变嵌合体。两个受影响的姐妹篇有一个突变，在他们的父母中检测不到，支持生殖系镶嵌。他们的父亲过去曾因睾丸癌接受过放射治疗。2只典型受累雌性有3只严重受累雌性胎仔，均存在中线胸壁和腹壁缺损，类似Cantrell五联征和肢体-体壁复合体。两名存活患者还存在胸腹壁缺损。PORCN突变也可能导致Cantrell五联症和肢体-体壁复合体。因此，特别是在肢体缺陷的情况下，它似乎是有用的搜索thes.Conclusions：PORCN突变可以发现在所有经典的受影响的情况下Goltz-Gorlin综合征，包括男性。发生体细胞和生殖细胞嵌合现象。基因型与表型无明显相关性。
Background: Goltz-Gorlin syndrome or focal dermal hypoplasia is a highly variable, X-linked dominant syndrome with abnormalities of ectodermal and mesodermal origin. In 2007, mutations in the PORCN gene were found to be causative in Goltz-Gorlin syndrome.Method: A series of 17 patients with Goltz-Gorlin syndrome is reported on, and their phenotype and genotype are described.Results: In 14 patients (13 females and one male), a PORCN mutation was found. Mutations included nonsense (n = 5), frameshift (n = 2), aberrant splicing (n = 2) and missense (n = 5) mutations. No genotype-phenotype correlation was found. All patients with the classical features of the syndrome had a detectable mutation. In three females with atypical signs, no mutation was found. The male patient had classical features and showed mosaicism for a PORCN nonsense mutation in fibroblasts. Two affected sisters had a mutation not detectable in their parents, supporting germline mosaicism. Their father had undergone radiation for testicular cancer in the past. Two classically affected females had three severely affected female fetuses which all had midline thoracic and abdominal wall defects, resembling the pentalogy of Cantrell and the limb-body wall complex. Thoracic and abdominal wall defects were also present in two surviving patients. PORCN mutations can possibly cause pentalogy of Cantrell and limb-body wall complexes as well. Therefore, particularly in cases with limb defects, it seems useful to search for these.Conclusions: PORCN mutations can be found in all classically affected cases of Goltz-Gorlin syndrome, including males. Somatic and germline mosaicism occur. There is no evident genotype-phenotype correlation.