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.
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.
Taillandier
A
A
Centre d'Etudes de Biologie Prénatale-SESEP, Université de Versailles, Versailles, France.
Cozien
E
E
Muller
F
F
Merrien
Y
Y
Bonnin
E
E
Fribourg
C
C
Simon-Bouy
B
B
Serre
J L
JL
Bieth
E
E
Brenner
R
R
Cordier
M P
MP
De Bie
S
S
Fellmann
F
F
Freisinger
P
P
Hesse
V
V
Hennekam
R C
RC
Josifova
D
D
Kerzin-Storrar
L
L
Leporrier
N
N
Zabot
M T
MT
Mornet
E
E
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
D000469:Alkaline Phosphatase