Congenital Corneal Endothelial Dystrophies Resulting From Novel De Novo Mutations.
Congenital Corneal Endothelial Dystrophies Resulting From Novel De Novo Mutations.
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DOI：
10.1097/ico.0000000000000670
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发表时间：
2016-02
期刊：
影响因子：
2.8
通讯作者：
Mootha VV
中科院分区：
文献类型：
--
作者：
Cunnusamy K;Bowman CB;Beebe W;Gong X;Hogan RN;Mootha VV
描述两例由新的新生突变引起的先天性角膜内皮水肿。病例A患者是一名15个月大的白人婴儿，病例B患者是一名3岁的西班牙裔儿童，自出生以来就出现双侧角膜混浊。临床病理结果。通过桑格测序筛选DNA样品中的候选基因突变。病例A的裂隙灯检查显示间质水肿和混浊。角膜移植纽扣的组织学显示基质增厚伴内皮细胞丢失和后弹力层变薄。桑格测序通过检测SLC 4A11中的复合杂合突变建立了先天性遗传性内皮营养不良（CHED）的诊断。先证者在一个SLC4A11等位基因中显示了一个新的从头移码突变，p。（Pro817Argfs*32），连同SLC4A11中的母系遗传错义突变，p.（Arg869His）。病例B患者同样表现为基质水肿和基质混浊。组织学分析显示海绵状上皮、Bowman层局灶性不连续性、基质增厚伴致密后基质区、后弹力膜厚度可变和区域多层内皮。桑格测序发现ZEB 1基因第一外显子存在一个新的无义突变，p. (Cys7*).据我们所知，我们目前最早的临床表现后多形性角膜营养不良导致的从头突变ZEB1。此外，我们提出了一个CHED的情况下，薄后弹力膜与一个新的复合杂合SLC4A11突变。在没有家族史或血缘关系的情况下，新生突变可能导致先天性角膜内皮营养不良。
To describe two cases of congenital corneal endothelial edema resulting from novel de novo mutations. Case A patient was a 15 months old Caucasian infant and Case B patient was a 3 year old Hispanic child presenting with bilateral cloudy corneas since birth. Clinicopathological findings are presented. DNA samples were screened for mutations in candidate genes by Sanger sequencing. Slit-lamp examination of Case A patient revealed stromal edema and haze. Histology of keratoplasty button showed stromal thickening with loss of endothelium and thin Descemet’s membrane. Sanger sequencing established the diagnosis of congenital hereditary endothelial dystrophy (CHED) by detection of a compound heterozygous mutation in SLC4A11. The proband displayed a novel de novo frameshift mutation in one SLC4A11 allele, p.(Pro817Argfs*32), in conjunction with a maternally inherited missense mutation in SLC4A11, p.(Arg869His). Case B patient similarly presented with stromal edema and stromal haze. Histopathological analysis revealed a spongy epithelium, focal discontinuities in Bowman’s layer, stromal thickening with areas of compacted posterior stroma, variable thickness of Descemet’s membrane, and regional multilayered endothelium. Sanger sequencing found a novel de novo nonsense mutation in the first exon of ZEB1, p.(Cys7*). To our knowledge, we present the earliest clinical presentation of posterior polymorphous corneal dystrophy resulting from a de novo mutation in ZEB1. Additionally, we present a CHED case with a thin Descemet’s membrane with a novel compound heterozygous SLC4A11 mutation. In the absence of a family history or consanguinity, de novo mutations may result in congenital corneal endothelial dystrophies.