Defective LFNG causes SCDO3

The Fringe family (CAZy family GT31) of glycosyltransferases in mammals includes LFNG (lunatic fringe; MIM:602576), MFNG (manic fringe; MIM:602577) and RFNG (radical fringe; MIM:602578). Fringe enzymes function in the Golgi apparatus where they initiate the elongation of O-linked fucose on fucosylated peptides by the addition of a beta 1,3 N-acetylglucosaminyl group (GlcNAc) (Moloney et al. 2000). Fringe enzymes elongate conserved O fucosyl residues conjugated to EGF repeats of NOTCH, modulating NOTCH activity (Cohen et al. 1997, Johnston et al. 1997) by decreasing the affinity of NOTCH extracellular domain for JAG ligands (Bruckner et al. 2000).<br><br>The spondylocostal dysostoses (SCDs) are a group of disorders that arise during embryonic development by a disruption of somitogenesis. The Notch signalling pathway is essential for somitogenesis, the precursors of vertebra and associated musculature. Defects in one of the Fringe enzymes, beta-1,3-N-acetylglucosaminyltransferase lunatic fringe (LFNG), can cause spondylocostal dysostosis, autosomal recessive 3 (SCDO3, MIM:609813), a condition of variable severity associated with vertebral and rib segmentation defects (Sparrow et al. 2006).

哺乳动物中，糖基转移酶的 Fringe 家族（CAZy 家族 GT31）包括 LFNG（lunatic fringe；MIM:602576）、MFNG（manic fringe；MIM:602577）和 RFNG（radical fringe；MIM:602578）。Fringe 酶在高尔基体中发挥作用，通过添加 β 1,3-乙酰氨基葡萄糖（GlcNAc）基团，启动 O-连接岩藻糖在岩藻酰化肽上的延长作用（Moloney 等人，2000年）。Fringe 酶延长与 NOTCH 的 EGF 重复序列共轭的保守 O-岩藻糖残基，通过降低 NOTCH 膜外结构域对 JAG 配体的亲和力，调节 NOTCH 的活性（Cohen 等人，1997年，Johnston 等人，1997年）。脊椎骨骨发育不良（spondylocostal dysostoses，SCDs）是一组在胚胎发育期间由于节生发生紊乱而引起的疾病。Notch 信号通路对于节生发生，即脊椎和关联肌肉的前体至关重要。Fringe 酶之一，β-1,3-乙酰氨基葡萄糖基转移酶 lunatic fringe（LFNG）的缺陷可导致脊椎骨骨发育不良，常染色体隐性 3 型（SCDO3，MIM:609813），这是一种与脊椎和肋骨节段性缺陷相关的疾病，其严重程度各异（Sparrow 等人，2006年）。