To the best of our knowledge, our genetic study represents the first reporting of a so high mutation rate in an Italian HPP cohort: it follows our previous work on a smaller survey (34) and describes a total of 23 molecularly confirmed HPP cases, 8 novel ALPL variants, 1 large ALPL deletion, and 1 case with familial hypophosphatasemia in which the search for the molecular basis has to date been unsuccessful. The gene discussed is ALPL; the disease is hypophosphatasia.