Fifteen new mutations (-195C>T, L-12X, 298-2A>G, T117N, A159T, R229S, 997+2T>A, E274X, A331T, H364R, D389G, 1256delC, R433H, N461I, C472S) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene in patients with hypophosphatasia

Hum Mutat. 2000 Mar;15(3):293. doi: 10.1002/(SICI)1098-1004(200003)15:3<293::AID-HUMU11>3.0.CO;2-Q.


Hypophosphatasia is a rare inherited disorder characterized by defective bone mineralization and deficiency of serum and liver/bone/kidney-type alkaline phosphatase (L/B/K ALP) activity. We report the characterization of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 12 families affected by severe or mild hypophosphatasia. Twenty distinct mutations were found, 5 of which were previously reported. Nine of the 15 new mutations were missense mutations (T117N, A159T, R229S, A331T, H364R, D389G, R433H, N461I, and C472S). The others were 2 nonsense mutations (L-12X and E274X), one single nucleotide deletion (1256delC), 2 mutations affecting splicing (298-2A>G, 997+2T>A), and a mutation in the major transcription start site (-195C>T). Hum Mutat 15:293, 2000.

MeSH terms

  • Alkaline Phosphatase / genetics*
  • Child
  • Female
  • Humans
  • Hypophosphatasia / enzymology*
  • Hypophosphatasia / genetics*
  • Infant
  • Male
  • Mutation
  • Mutation, Missense
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational


  • Alkaline Phosphatase