A case of autosomal dominant osteopetrosis type II with a severe bone phenotype but no amino acid converting mutation in the CLCN7 gene
Abstract
Autosomal Dominant Osteopetrosis type II (ADOII), also known as Albers-Schonberg disease, is caused by mutation of the CLCN7 chloride channel gene and is characterized by reduced bone resorption. Here we report on an individual with the classic features of ADOII, who had a history of fractures from childhood, displayed high bone mass and characteristic sandwich vertebrae on x-ray. Our genetic analyses showed no amino acid converting mutation in the patients DNA but we did find evidence of haploinsufficiency of CLCN7 mRNA. An iliac crest bone sample from the patient revealed bone tissue and material abnormalities relative to normal controls based on quantitative backscattered electron imaging and histomorphometric analyses. Additionally to lamellar bone, we observed significant amounts of woven bone and mineralised cartilage, as well as an increased frequency and thickness (up to 15 microns) of cement lines. Giant osteoclasts with numerous nuclei were present. The bone mineralisation density distribution (BMDD) of the entire bone area revealed markedly increased average mineral content of the dense bone (CaMean T-score +10.1) and frequency of bone with highest mineral content (CaHigh T-score +19.6), suggesting continued mineral accumulation and lack of bone remodelling. Osteocyte lacunae sections (OLS) characteristics were unremarkable except the OLS shape which was unusually circular. Together, our findings suggest that the reduced expression of CLCN7 mRNA in osteoclasts,…
Read the paper
Related studies
- Characterization and Analysis of Porosity and Pore Structures
- Practical considerations for conducting ecotoxicity test methods with manufactured nanomaterials: what have we learnt so far?
- Dental Optical Coherence Tomography
- Radiation-shielding concrete: A review of materials, performance, and the impact of radiation on concrete properties
- Testing entanglement of annihilation photons
- Calanus finmarchicus seasonal cycle and diapause in relation to gene expression, physiology, and endogenous clocks
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.