Two novel nonsense mutations in GALNT3 gene are responsible for familial tumoral calcinosis

被引:32
作者
Barbieri, Anna Maria
Filopanti, Marcello
Bua, Guido
Beck-Peccoz, Paolo
机构
[1] Univ Milan, IRCCS, Fdn Policlin, Dept Med Sci,Endocrine & Metab Unit, I-20122 Milan, Italy
[2] Policlin Sassarese, Neurol Serv, Sassari, Italy
关键词
calcinosis; GALNT3; FGF23; mutation; phosphate;
D O I
10.1007/s10038-007-0126-5
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:464 / 468
页数:5
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