A New Heterozygous Mutation (R714C) of the Osteopetrosis Gene, <i>Pleckstrin Homolog Domain Containing Family M (With Run Domain) Member 1 (PLEKHM1)</i>, Impairs Vesicular Acidification and Increases TRACP Secretion in Osteoclasts

Abstract

We provide further evidence for a role of Plekhm-1 in osteoclasts by showing that a novel mutation in PLEKHM1 is associated with a complex bone phenotype of generalized osteopenia combined with "focal osteosclerosis." Our data suggest that the mutation affects endosomal acidification/maturation and TRACP exocytosis, with implications for osteoclast-osteoblast cross-talk.