Clinical utility gene card for: hypophosphatasia

Abstract

1.5 Mutational spectrum Over 200 different disease-causing mutations have been reported in the ALPL gene mutations. Database: http://www.sesep.uvsq.fr/03_hypo_mutations.php. The distribution is as follows: 79% missense mutations; 10% small deletions; 4% splicing mutations; 3% nonsense mutations; 2% small insertions; and r1%: complex insertion/deletions, large deletions and mutations in the regulatory sequence. The large proportion of missense mutations with various effects on the enzymatic activity of alkaline phosphatase has been correlated with the high clinical variability.1 A part of missense mutations exhibits a dominant-negative effect,2–5 explaining dominant inheritance of mild forms of the disease.6–8