Two novel nonsense mutations in GALNT3 gene are responsible for familial tumoral calcinosis
Two novel nonsense mutations in GALNT3 gene are responsible for familial tumoral calcinosis
复制标题
DOI：
10.1007/s10038-007-0126-5
复制
发表时间：
2007-05-01
影响因子：
3.5
通讯作者：
Beck-Peccoz, Paolo
中科院分区：
文献类型：
--
作者：
Barbieri, Anna Maria;Filopanti, Marcello;Beck-Peccoz, Paolo
异位关节周围钙化与血清磷酸盐水平升高相关是高磷血症家族性肿瘤钙化症（HFTC）的主要临床特征，HFTC是一种罕见的常染色体隐性代谢疾病。该疾病可由至少两种不同基因的隐性突变引起：GalNAc转移酶3 (GALNT3)，编码启动黏液型o糖基化的糖基转移酶，以及成纤维细胞生长因子23 (FGF23)，编码磷酸盐循环水平的调节因子。在目前的研究中，我们对一名HFTC患者及其亲属的GALNT3基因进行了突变分析。序列分析表明，该先证者为外显子4 （Y322X）和外显子7 （Q481X）两个新的无义突变的复合杂合子。通过聚合酶链反应限制性片段长度多态性（PCR-RFLP）分析证实突变与家族内疾病的共分离。这是首次报道GALNT3基因编码序列中同时存在两个不同的停止密码子。
Ectopic periarticular calcifications associated with elevated levels of serum phosphate represent the principal clinical features of hyperphosphatemic familial tumoral calcinosis (HFTC), a rare autosomal recessive metabolic disorder. The disease can be caused by recessive mutations in at least two different genes: GalNAc transferase 3 (GALNT3), encoding a glycosyltransferase that initiates mucin-type O-glycosylation, and fibroblast growth factor 23 (FGF23), which encodes a regulator of phosphate circulating levels. In the current study, we performed mutation analyses of the GALNT3 gene in a subject with HFTC and in his relatives. Sequence analyses revealed that the proband was a compound heterozygote for two novel nonsense mutations in exon 4 (Y322X) and in exon 7 (Q481X). Cosegregation of the mutations with the disease within the family was confirmed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. This is the first report describing the simultaneous presence of two different stop codons in the coding sequence of the GALNT3 gene.