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The osteopetrosis of ADO2 has been attributed to hypofunctional osteoclasts. The mechanism underlying the abnormality in osteoclast function remains largely unknown. This study was designed to investigate gene mutations and osteoclast function in a case that was clinically diagnosed as ADO2. Genomic DNA was extracted from blood samples of this patient, and the 25 exons of <jats:italic>CLCN7<\/jats:italic> were amplified. Peripheral blood from the ADO2 subject and a healthy age- and sex-matched control was used to evaluate osteoclastogenesis, osteoclast morphology, and bone resorption. Analysis of DNA from the patient showed a germline heterozygous missense mutation, c.1856C&gt;T (p.P619L), in exon 20 of <jats:italic>CLCN7<\/jats:italic>. A similar homozygous mutation at this site was previously reported in a patient with autosomal recessive osteopetrosis. When cultured, the peripheral blood mononuclear cells (PBMCs) from the ADO2 patient spontaneously differentiated into mature osteoclasts <jats:italic>in vitro<\/jats:italic>. The ADO2 patient\u2019s PBMCs formed enhanced, but heterogeneous, osteoclasts in both the presence and absence of macrophage-colony stimulating factor, and nuclear factor-\u0138B ligand. Bone resorption was reduced in the ADO2 patient\u2019s osteoclasts, which exhibited aberrant morphology and abnormal distribution of integrin a<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>. Gene analysis found increased <jats:italic>c-fos<\/jats:italic> expression and reduced <jats:italic>RhoA<\/jats:italic> and <jats:italic>integrin beta 3<\/jats:italic> expression in ADO2 cells. In conclusion, our data suggest that enhanced, heterogeneous osteoclast induction may be an intrinsic characteristic of ADO2.<\/jats:p>","DOI":"10.1038\/boneres.2016.35","type":"journal-article","created":{"date-parts":[[2016,11,29]],"date-time":"2016-11-29T11:29:08Z","timestamp":1480418948000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Enhanced but hypofunctional osteoclastogenesis in an autosomal dominant osteopetrosis type II case carrying a c.1856C&gt;T mutation in CLCN7"],"prefix":"10.1038","volume":"4","author":[{"given":"Xiang","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet","family":"Hock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunyu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xijie","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2016,11,29]]},"reference":[{"key":"BFboneres201635_CR1","doi-asserted-by":"publisher","first-page":"197","DOI":"10.3233\/BMR-140486","volume":"28","author":"AK Ozkan","year":"2015","unstructured":"Ozkan AK, Doruk P, Adam M et al. 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