Expanding the phenotypic spectrum of PORCN variants in two males with syndromic microphthalmia
Expanding the phenotypic spectrum of PORCN variants in two males with syndromic microphthalmia
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DOI：
10.1038/ejhg.2014.135
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发表时间：
2015-04-01
影响因子：
5.2
通讯作者：
Vermeesch, Joris R.
中科院分区：
文献类型：
--
作者：
Brady, Paul D.;Van Esch, Hilde;Vermeesch, Joris R.
PORCN的变异是Goltz-Gorlin综合征或局灶性皮肤发育不全的原因，这是一种影响杂合子女性的X连锁显性疾病，迄今为止被认为是男性的胚胎致死性疾病。在一个家族中进行外显子组测序，其中两个男性兄弟姐妹的特征是小眼球和其他先天性异常，包括疝气，脊柱裂和心脏缺陷。令人惊讶的是，我们确定了一个母系遗传的变异PORCN目前在两个男性以及两个女性同胞。这是首次在受Goltz-Gorlin综合征影响的非马赛克男性中发现PORCN变体。明显无症状的母亲表现出极端的X-失活的偏斜（90%），无症状的女性同胞表现出88%的偏斜，第二个女性同胞与头皮皮肤发育不全的影响显示X-失活认为在正常范围内。
Variants in PORCN are a cause of Goltz-Gorlin syndrome or Focal Dermal Hypoplasia, an X-linked dominant disorder affecting heterozygous females and until now considered to be embryonic lethal in males. Exome sequencing was performed in a family in which two male siblings were characterized by microphthalmia and additional congenital anomalies including diaphragmatic hernia, spina bifida and cardiac defects. Surprisingly, we identified a maternally inherited variant in PORCN present in both males as well as in two female siblings. This represents the first finding of a PORCN variant in non-mosaic males affected with Goltz-Gorlin syndrome. The apparently asymptomatic mother showed extreme skewing of X-inactivation (90%), an asymptomatic female sibling showed skewing of 88%, and the second female sibling affected with cutis aplasia of the scalp showed X-inactivation considered within the normal range.