Osteopetrosis, Autosomal Recessive 7

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Retrieved

2019-09-22

Source

Omim

Trials

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Genes

TNFRSF11A, SLC29A3

Drugs

Allogeneic multi-virus specific T lymphocytes targeting BK virus, cytomegalovirus, human herpesvirus-6, Epstein Barr virus and adenovirus, Interferon gamma 1b ( ACTIMMUNE, IMUKIN ), haematopoietic stem cells and blood progenitors umbilical cord-derived expanded with (1R, 4R)-N1-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl)cyclohexane-1,4-diamine dihydrobromide dihydrate

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A number sign (#) is used with this entry because of evidence that autosomal recessive osteopetrosis-7 (OPTB7) is caused by homozygous or compound heterozygous mutation in the TNFRSF11A gene (603499) on chromosome 18q21.

For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive osteopetrosis, see OPTB1 (259700).

Clinical Features

Guerrini et al. (2008) described 8 patients from 7 unrelated families with severe osteoclast-poor osteopetrosis, 1 of whom (patient 2) was an Argentinian male infant who had previously been studied by Blair et al. (2004) (subject 2). Serum immunoglobulin levels were found to be reduced in 3 of 4 patients who underwent assessment; 2 of the 3 hypogammaglobulinemic patients failed to produce antibodies after a full course of tetanus toxoid vaccination. Bone biopsy specimens from 3 patients showed extensive trabecular structures, with retention of large areas of cartilage, complete absence of multinucleated cells, and lack of osteoclastic resorption; in 1 patient, the possible presence of small mononuclear osteoclasts was excluded by histochemical staining for tartrate-resistant acid phosphatase (TRAP).

Hanada et al. (2009) reported that 2 patients with the arg170-to-gly mutation (603499.0003) had a markedly abrogated fever response with severe pneumonia, confirmed by serology and chest x-ray. Hanada et al. (2009) demonstrated an essential role for RANK and RANKL (602642) in female thermoregulation and the central fever response in inflammation.

Molecular Genetics

In 8 patients with osteoclast-poor osteopetrosis from 7 unrelated families, who were known to lack mutations in genes associated with autosomal recessive osteopetrosis, Guerrini et al. (2008) identified homozygosity or compound heterozygosity for 7 different mutations in the TNFRSF11A gene (see, e.g., 603499.0003-603499.0007). The authors noted that the osteopetrosis in these patients could be rescued by hematopoietic stem cell transplantation, in contrast to that of patients with TNFSF11 (602642) deficiency (see OPTB2; 259710).