title: 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.
abstract: 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.
authors.affiliation: Centre d'Etudes de Biologie Prénatale-SESEP, Université de Versailles, Versailles, France.
authors.forename: A
authors.initials: A
authors.lastname: Taillandier
authors.forename: E
authors.initials: E
authors.lastname: Cozien
authors.forename: F
authors.initials: F
authors.lastname: Muller
authors.forename: Y
authors.initials: Y
authors.lastname: Merrien
authors.forename: E
authors.initials: E
authors.lastname: Bonnin
authors.forename: C
authors.initials: C
authors.lastname: Fribourg
authors.forename: B
authors.initials: B
authors.lastname: Simon-Bouy
authors.forename: J L
authors.initials: JL
authors.lastname: Serre
authors.forename: E
authors.initials: E
authors.lastname: Bieth
authors.forename: R
authors.initials: R
authors.lastname: Brenner
authors.forename: M P
authors.initials: MP
authors.lastname: Cordier
authors.forename: S
authors.initials: S
authors.lastname: De Bie
authors.forename: F
authors.initials: F
authors.lastname: Fellmann
authors.forename: P
authors.initials: P
authors.lastname: Freisinger
authors.forename: V
authors.initials: V
authors.lastname: Hesse
authors.forename: R C
authors.initials: RC
authors.lastname: Hennekam
authors.forename: D
authors.initials: D
authors.lastname: Josifova
authors.forename: L
authors.initials: L
authors.lastname: Kerzin-Storrar
authors.forename: N
authors.initials: N
authors.lastname: Leporrier
authors.forename: M T
authors.initials: MT
authors.lastname: Zabot
authors.forename: E
authors.initials: E
authors.lastname: Mornet
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D007014:Hypophosphatasia / Q000201:enzymology* / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational
chemical_list: D000469:Alkaline Phosphatase