Department of Biotechnology and Genetic Engineering, Philadelphia University, Amman, Jordan.
Dr. Med. Sight and Insight Eye Clinic, Amman, Jordan.
Curr Mol Med. 2019;19(9):683-687. doi: 10.2174/1566524019666190730095630.
Keratoconus (KC) is usually bilateral, noninflammatory progressive corneal ectasia in which the cornea becomes progressively thin and conical. Despite the strong evidence of genetic contribution in KC, the etiology of KC is not understood in most cases.
In this study, we used whole-exome sequencing to identify the genetic cause of KC in two sibs in a consanguineous family. The Homozygous frameshift variant NM_001253826.1:c.60delC;p.Leu21Cysfs*6 was identified in the gene Nacetylgalactosaminyltransferase 14 (GALNT14). The variant does not exist in all public databases neither in our internal exome database. Moreover, no database harbours homozygous loss of function variants in the candidate gene.
GALNT14 catalyses the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D- galactosamine residue to a serine or threonine residue on target proteins especially Mucins.
As alterations of mucin's glycosylation are linked to a number of eye diseases, we demonstrate in this study an association between the truncated protein GALNT14 and KC.
圆锥角膜（KC）通常是双侧的、非炎症性的进行性角膜扩张，其中角膜逐渐变薄并呈圆锥形。尽管 KC 具有很强的遗传贡献证据，但在大多数情况下，KC 的病因仍不清楚。
在这项研究中，我们使用全外显子组测序来鉴定一个近亲家庭中两名同胞的 KC 的遗传原因。在基因 N-乙酰半乳糖胺转移酶 14（GALNT14）中发现了 NM_001253826.1：c.60delC;p.Leu21Cysfs*6 纯合移码变异。该变异既不存在于所有公共数据库中，也不存在于我们的内部外显子组数据库中。此外，候选基因中没有数据库包含纯合失活变异。
GALNT14 催化 O-连接寡糖生物合成的初始反应，将 N-乙酰-D-半乳糖胺残基转移到靶蛋白（特别是粘蛋白）上的丝氨酸或苏氨酸残基上。
由于粘蛋白糖基化的改变与许多眼部疾病有关，我们在这项研究中证明了截断蛋白 GALNT14 与 KC 之间存在关联。
