title: Characterization of missense mutations and large deletions in the ALPL gene by sequencing and quantitative multiplex PCR of short fragments.
abstract: 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.
authors.affiliation: Laboratoire SESEP, Université de Versailles Saint Quentin en Yvelines, Versailles, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Spentchian
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brun-Heath
authors.forename: Agnès
authors.initials: A
authors.lastname: Taillandier
authors.forename: Delphine
authors.initials: D
authors.lastname: Fauvert
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Serre
authors.forename: Brigitte
authors.initials: B
authors.lastname: Simon-Bouy
authors.forename: Filipa
authors.initials: F
authors.lastname: Carvalho
authors.forename: Ilga
authors.initials: I
authors.lastname: Grochova
authors.forename: Sarju G
authors.initials: SG
authors.lastname: Mehta
authors.forename: Grit
authors.initials: G
authors.lastname: Müller
authors.forename: Saskia Lesnik
authors.initials: SL
authors.lastname: Oberstein
authors.forename: Gonul
authors.initials: G
authors.lastname: Ogur
authors.forename: Saba
authors.initials: S
authors.lastname: Sharif
authors.forename: Etienne
authors.initials: E
authors.lastname: Mornet
mesh_terms: 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
chemical_list: D000469:Alkaline Phosphatase