Defective GALNT3 causes HFTC

The family of UDP GalNAc:polypeptide N acetylgalactosaminyltransferases (GalNAc transferases, GALNTs) carry out the addition of N acetylgalactosamine (GalNAc) on serine, threonine or possibly tyrosine residues on a wide variety of proteins, most commonly associated with mucins. This is the initial reaction in the biosynthesis of GalNAc-type O linked oligosaccharides (Wandall et al. 1997). This reaction takes place in the Golgi apparatus (Rottger et al. 1998). There are 20 known members of the GALNT family, 15 of which have been characterised and 5 candidate members which are thought to belong to this family based on sequence similarity (Bennett et al. 2012). The GALNT-family is classified as belonging to CAZy family GT27. Defects in one of the GALNT family genes, GALNT3 (MIM:601756), can cause familial hyperphosphatemic tumoral calcinosis (HFTC; MIM:211900). HFTC is a rare autosomal recessive severe metabolic disorder characterised by the progressive deposition of calcium phosphate crystals in the skin, soft tissues and sometimes bone (Chefetz et al. 2005). The biochemical observation is hyperphosphatemia, caused by increased renal absorption of phosphate (Chefetz et al. 2005, Ichikawa et al. 2005). Some patients manifest recurrent, transient, painful swellings of the long bones with radiological evidence of periosteal reaction and cortical hyperostosis (Frishberg et al. 2005).

UDP 葡萄糖胺酰聚糖：多肽 N 乙酰半乳糖胺基转移酶（乙酰半乳糖胺基转移酶，GALNTs）家族负责在多种蛋白质的丝氨酸、苏氨酸或可能酪氨酸残基上添加 N 乙酰半乳糖胺（GalNAc），此过程与粘蛋白最为常见。这构成了 GalNAc 型 O 连接寡糖生物合成过程中的初始反应（Wandall 等人，1997 年）。该反应发生在高尔基体中（Rottger 等人，1998 年）。已知该家族有 20 个成员，其中 15 个已被鉴定，另外 5 个成员基于序列相似性被认为属于该家族（Bennett 等人，2012 年）。GALNT 家族被归类为属于 CAZy 家族 GT27。GALNT 家族中某一基因（GALNT3，MIM：601756）的缺陷可导致家族性高磷酸血症肿瘤性钙化病（HFTC；MIM：211900）。HFTC 是一种罕见的常染色体隐性严重代谢障碍，其特征为皮肤、软组织和有时骨骼中磷酸钙晶体的进行性沉积（Chefetz 等人，2005 年）。生化观察发现高磷酸血症，这是由于肾脏对磷酸的吸收增加所致（Chefetz 等人，2005 年，Ichikawa 等人，2005 年）。一些患者表现为长骨反复、短暂的、疼痛性肿胀，伴有放射学上骨膜反应和皮质增生症的证据（Frishberg 等人，2005 年）。