AP-HP, Hôpital Jean Verdier, Service d'Histologie, Embryologie, et Cytogénétique, Bondy, France.
Am J Med Genet A. 2012 Oct;158A(10):2430-8. doi: 10.1002/ajmg.a.35548. Epub 2012 Aug 17.
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.
FOXC1 缺失、重复和突变与 Axenfeld-Rieger 异常和 Dandy-Walker 畸形谱有关。我们描述了三个胎儿、两个儿童和一个成人的临床病史、体格检查结果和可获得的脑部影像学研究，这些患者均存在包含 FOXC1 的 6p25 缺失。发现了各种眼部和小脑畸形的组合。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，显示出前节段眼部发育不良，提示 Axenfeld-Rieger 异常。五个 6p25 缺失为末端缺失，包括两个源自遗传相互易位的缺失；其余的 6p25 缺失为中间缺失。这些缺失的大小和断点使用比较基因组杂交阵列进行了特征描述。所有六个缺失均包含 FOXC1。我们的数据证实，FOXC1 杂合不足在 6p25 缺失患者的表型中起主要作用。Axenfeld-Rieger 异常的组织病理学特征在妊娠第三个三个月开始之前就可以清楚地识别出来。
