Characterization of missense mutations and large deletions in the ALPL gene by sequencing and quantitative multiplex PCR of short fragments.
Hypophosphatasia is a rare inherited bone disorder characterized by defective bone and dental mineralization and deficiency of serum and liver/bone/kidney alkaline phosphatase activity. The disease is due to mutations in the alkaline phosphatase liver-type (ALPL) gene. Gross deletions or insertions have not previously been reported in this gene. We report here the characterization of nine novel ALPL gene mutations in a series of 8 patients affected by various forms of hypophosphatasia. The newly discovered mutations included five missense mutations (c.368C --> A, c.814C--> T, c.1196C--> T, c.1199C--> T, c.1283G--> C), two small deletions (c.797_802del, c.1044_1055del), and two large deletions. The large deletions were detected by quantitative multiplex polymerase chain reaction (PCR) of short fluorescent fragments (QMPSF). We conclude that QMPSF slightly reduces the proportion of undetected mutations in hypophosphatasia and improves genetic counselling in the affected families.
Spentchian
Marc
M
Laboratoire SESEP, Université de Versailles Saint Quentin en Yvelines, Versailles, France.
Brun-Heath
Isabelle
I
Taillandier
Agnès
A
Fauvert
Delphine
D
Serre
Jean-Louis
JL
Simon-Bouy
Brigitte
B
Carvalho
Filipa
F
Grochova
Ilga
I
Mehta
Sarju G
SG
Müller
Grit
G
Oberstein
Saskia Lesnik
SL
Ogur
Gonul
G
Sharif
Saba
S
Mornet
Etienne
E
D000293:Adolescent; D000469:Alkaline Phosphatase / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007014:Hypophosphatasia / Q000175:diagnosis* / Q000235:genetics; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction / Q000379:methods*; D011247:Pregnancy; D011296:Prenatal Diagnosis
D000469:Alkaline Phosphatase