PDF(Pubmed)
Abstract：
Variations in the protocadherin gene FAT1 have recently been associated with a syndrome that includes coloboma, facial dysmorphism, renal failure, syndactyly, and other developmental defects.
Detailed medical and family history, physical examination, and molecular analysis.
This non-dysmorphic, intellectually normal 51-year-old woman presented with bilateral colobomata and renal failure of unclear etiology, and asymmetric sensorineural hearing loss. Family history was notable for multiple family members with various forms of cancer. Whole exome sequencing revealed a homozygous frame shift variant in FAT1, predicted to truncate the FAT1 protein at the furthest position in the protein structure published to date in a patient with coloboma.
This case provides further evidence of the pleiotropic effects of FAT1 in optic fissure closure and kidney function. Also, because this variant is in the last exon, it would be anticipated to escape nonsense-mediated decay, opening the possibility that the protein is made and expressed, but not completely functional, as its intracellular domain is truncated.
Detailed medical and family history, physical examination, and molecular analysis.
This non-dysmorphic, intellectually normal 51-year-old woman presented with bilateral colobomata and renal failure of unclear etiology, and asymmetric sensorineural hearing loss. Family history was notable for multiple family members with various forms of cancer. Whole exome sequencing revealed a homozygous frame shift variant in FAT1, predicted to truncate the FAT1 protein at the furthest position in the protein structure published to date in a patient with coloboma.
This case provides further evidence of the pleiotropic effects of FAT1 in optic fissure closure and kidney function. Also, because this variant is in the last exon, it would be anticipated to escape nonsense-mediated decay, opening the possibility that the protein is made and expressed, but not completely functional, as its intracellular domain is truncated.
摘要：
■原钙粘蛋白基因FAT1的变异最近与包括结肠瘤的综合征有关，面部畸形,肾功能衰竭,齐体,和其他发育缺陷。
■详细的病史和家族史，体检,和分子分析。
■这种非畸形，智力正常的51岁女性表现为双侧结瘤和病因不明的肾衰竭，和不对称的感觉神经性听力损失。家族史对于患有各种形式癌症的多个家庭成员是值得注意的。全外显子组测序揭示了FAT1中的纯合移码变体，预测将在迄今为止发表的结肠瘤患者的蛋白质结构中最远的位置截短FAT1蛋白质。
■该病例提供了FAT1在视裂闭合和肾功能中的多效性作用的进一步证据。此外，因为这个变体在最后一个外显子中，它可以避免胡说八道介导的衰变，打开蛋白质被制造和表达的可能性，但不是完全的功能，因为它的胞内结构域被截断。
■详细的病史和家族史，体检,和分子分析。
■这种非畸形，智力正常的51岁女性表现为双侧结瘤和病因不明的肾衰竭，和不对称的感觉神经性听力损失。家族史对于患有各种形式癌症的多个家庭成员是值得注意的。全外显子组测序揭示了FAT1中的纯合移码变体，预测将在迄今为止发表的结肠瘤患者的蛋白质结构中最远的位置截短FAT1蛋白质。
■该病例提供了FAT1在视裂闭合和肾功能中的多效性作用的进一步证据。此外，因为这个变体在最后一个外显子中，它可以避免胡说八道介导的衰变，打开蛋白质被制造和表达的可能性，但不是完全的功能，因为它的胞内结构域被截断。
