Albers-Schönberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene

Hum Mol Genet. 2001 Dec 1;10(25):2861-7. doi: 10.1093/hmg/10.25.2861.


Albers-Schönberg disease, or autosomal dominant osteopetrosis, type II (ADO II), is the most common form of osteopetrosis, a group of conditions characterized by an increased skeletal mass due to impaired bone and cartilage resorption. Following the assignment of the gene causing ADO II to chromosome 16p13.3, we now report seven different mutations in the gene encoding the ClCN7 chloride channel in all 12 ADO II families analysed. Additionally, a patient with the severe, autosomal recessive, infantile form of osteopetrosis (ARO) was identified as being homozygous for a ClCN7 mutation. From genotype-phenotype correlations, it seems that ADO II reflects a dominant negative effect, whereas loss-of-function mutations in ClCN7 do not cause abnormalities in heterozygous individuals. Because some ARO patients have mutations in both copies of the ClCN7 gene, ADO II is allelic with a subset of ARO cases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Chloride Channels / genetics*
  • Chromosomes, Human, Pair 16
  • DNA Mutational Analysis
  • DNA Primers / chemistry
  • Female
  • Genes, Dominant
  • Haplotypes
  • Humans
  • Infant
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Osteopetrosis / diagnostic imaging
  • Osteopetrosis / genetics*
  • Pedigree
  • Peptide Fragments / chemistry
  • Polymerase Chain Reaction
  • Radiography
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques


  • CLCN7 protein, human
  • Chloride Channels
  • DNA Primers
  • Peptide Fragments

Associated data

  • GENBANK/AL031600
  • GENBANK/AL031705
  • OMIM/166600
  • OMIM/259700
  • OMIM/259710
  • OMIM/259730