Cleiren et al. (2001) reported a girl, born to second-cousin parents of Chinese ancestry, who presented at 3 months of age with Bell palsy. Radiographic skeletal survey revealed severe osteopetrosis and several nondisplaced oblique fractures. She had anemia, ... Cleiren et al. (2001) reported a girl, born to second-cousin parents of Chinese ancestry, who presented at 3 months of age with Bell palsy. Radiographic skeletal survey revealed severe osteopetrosis and several nondisplaced oblique fractures. She had anemia, reticulocytosis, hepatosplenomegaly, and mild optic nerve atrophy. The child underwent a mismatched allogeneic marrow transplant but died at age 18 months from sepsis and respiratory failure.
Based on the similarity between the phenotype of patients with infantile malignant osteopetrosis and that of mice with targeted disruption of the Clcn7 gene (see 602727), which develop severe osteopetrosis and retinal degeneration, Kornak et al. (2001) searched ... Based on the similarity between the phenotype of patients with infantile malignant osteopetrosis and that of mice with targeted disruption of the Clcn7 gene (see 602727), which develop severe osteopetrosis and retinal degeneration, Kornak et al. (2001) searched for mutations in the human CLCN7 gene in 12 patients with infantile osteopetrosis. They identified compound heterozygosity for a nonsense (Q555X; 602727.0001) and a missense (R762Q; 602727.0002) mutation in the CLCN7 gene in 1 patient with infantile malignant osteopetrosis who had early visual impairment. No retinal histology was available. In a girl with severe autosomal recessive infantile osteopetrosis born to consanguineous parents of Chinese ancestry, Cleiren et al. (2001) identified homozygosity for a missense mutation (L766P; 602727.0003) in the CLCN7 gene. Her parents, who were heterozygous for the mutation, were asymptomatic, but radiographic skeletal survey was unavailable. Because OPTB4 patients are homozygous whereas patients with autosomal dominant osteopetrosis-2 (OPTA2; 166600) are heterozygous for mutations in CLCN7, the 2 disorders appear to be allelic. Cleiren et al. (2001) hypothesized that OPTA2 reflects a dominant negative effect, since loss-of-function mutations in CLCN7 do not cause abnormalities in heterozygous individuals. Lam et al. (2007) investigated a patient with malignant osteopetrosis, the daughter of consanguineous parents, using whole genome scans based on high density single-nucleotide polymorphism (SNP) microarray for homozygosity mapping. Mapping revealed that among the 3 possible causal loci, only the CLCN7 gene was located in an autozygous region. Mutation analysis of the CLCN7 gene showed that the proband was homozygous for a novel missense mutation (I261F; 602727.0006).