Severe hypophosphatasia: characterization of fifteen novel mutations in the ALPL gene.
Hypophosphatasia is an inherited disorder characterized by defective bone mineralization and deficiency of serum and tissue liver/bone/kidney alkaline phosphatase (L/B/K ALP) activity. We report the characterization of ALPL gene mutations in a series of 11 families from various origins affected by perinatal and infantile hypophosphatasia. Sixteen distinct mutations were found, fifteen of them not previously reported: M45V, G46R, 388-391delGTAA, 389delT, T131I, G145S, D172E, 662delG, G203A, R255L, 876-881delAGGGGA, 962delG, E294K, E435K, and A451T. This confirms that severe hypophosphatasia is due to a large spectrum of mutations in Caucasian populations.
Spentchian
M
M
Centre d'Etudes de Biologie Prénatal-SESEP, Université de Versailles-Saint Quentin en Yvelines, Versailles, France.
Merrien
Y
Y
Herasse
M
M
Dobbie
Z
Z
Gläser
D
D
Holder
S E
SE
Ivarsson
S-A
SA
Kostiner
D
D
Mansour
S
S
Norman
A
A
Roth
J
J
Stipoljev
F
F
Taillemite
J-L
JL
van der Smagt
J J
JJ
Serre
J-L
JL
Simon-Bouy
B
B
Taillandier
A
A
Mornet
E
E
D000469:Alkaline Phosphatase / Q000235:genetics*; D005260:Female; D006801:Humans; D007014:Hypophosphatasia / Q000175:diagnosis / Q000201:enzymology* / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D015997:Neonatal Screening; D011247:Pregnancy; D011296:Prenatal Diagnosis
D000469:Alkaline Phosphatase