Pre- and Postnatal Phenotype of 6p25 Deletions Involving the FOXC1 Gene
Pre- and Postnatal Phenotype of 6p25 Deletions Involving the FOXC1 Gene
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DOI：
10.1002/ajmg.a.35548
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发表时间：
2012-10-01
影响因子：
2
通讯作者：
Pipiras, Eva
中科院分区：
文献类型：
--
作者：
Delahaye, Andree;Khung-Savatovsky, Suonavy;Pipiras, Eva
FOXC1缺失、重复和突变与Ahenfeld-Rieger畸形和Dandy-Walker畸形谱相关。我们描述了三名胎儿、两名儿童和一名成人的临床病史、物理发现和可用的脑成像研究，其中包括FOXC1基因6p25缺失。眼睛和小脑畸形的各种组合被发现。在所有三个胎儿中，尸检包括对眼睛和大脑的详细显微镜评估，显示眼前段发育不全，提示为阿森菲尔德-里格畸形。5个6p25缺失为末端，其中2个来自遗传性相互易位，其余6p25缺失为间质缺失。使用比较基因组杂交阵列来表征这些缺失的大小和断裂点。所有六个缺失都包括FOXC1。我们的数据证实FOXC1单倍体不足在6p25缺失患者的表型中起主要作用。阿森菲尔德-里格异常的组织病理学特征在妊娠晚期开始之前就可以清楚地识别出来。(C)2012年威利期刊公司。
FOXC1 deletion, duplication, and mutations are associated with Axenfeld-Rieger anomaly, and Dandy-Walker malformation spectrum. We describe the clinical history, physical findings, and available brain imaging studies in three fetuses, two children, and one adult with 6p25 deletions encompassing FOXC1. Various combinations of ocular and cerebellar malformations were found. In all three fetuses, necropsy including detailed microscopic assessments of the eyes and brains showed ocular anterior segment dysgenesis suggestive of Axenfeld-Rieger anomaly. Five 6p25 deletions were terminal, including two derived from inherited reciprocal translocations; the remaining 6p25 deletion was interstitial. The size and breakpoints of these deletions were characterized using comparative genomic hybridization arrays. All six deletions included FOXC1. Our data confirm that FOXC1 haploinsufficiency plays a major role in the phenotype of patients with 6p25 deletions. Histopathological features of Axenfeld-Rieger anomaly were clearly identifiable before the beginning of the third-trimester of gestation. (C) 2012 Wiley Periodicals, Inc.