Long-term survival in infantile malignant autosomal recessive osteopetrosis secondary to homozygous p.Arg526Gln mutation in CLCN7

Authors

  • Piranit Nik Kantaputra,

    Corresponding author
    1. Faculty of Dentistry, Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Craniofacial Genetics Laboratory, Chiang Mai University, DENTALAND CLINIC, Chiang Mai, Thailand
    • Craniofacial Genetics Laboratory, Faculty of Dentistry, Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Chiang Mai University, DENTALAND CLINIC, Chiang Mai, Thailand.
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  • Saranya Thawanaphong,

    1. Faculty of Dentistry, Division of Periodontology, Department of Restorative Dentistry and Periodontology, Chiang Mai University, Chiang Mai, Thailand
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  • Witchapong Issarangporn,

    1. Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Chiang Mai University, Chiang Mai, Thailand
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  • Phennapha Klangsinsirikul,

    1. Faculty of Associated Medical Sciences, Division of Transfusion Science, Department of Medical Technology, Chiang Mai University, Chiang Mai, Thailand
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  • Atsushi Ohazama,

    1. Department of Craniofacial Development and NIHR Comprehensive Biomedical Research Centre, King's College London, Guy's Hospital, London Bridge, London, UK
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  • Paul Sharpe,

    1. Department of Craniofacial Development and NIHR Comprehensive Biomedical Research Centre, King's College London, Guy's Hospital, London Bridge, London, UK
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  • Chayarop Supanchart

    1. Faculty of Dentistry, Department of Oral and Maxillofacial Surgery, Chiang Mai University, Chiang Mai, Thailand
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  • How to Cite this Article: Kantaputra PN, Thawanaphong S, Issarangporn W, Klangsinsirikul P, Ohazama A, Sharpe P, Supanchart C. 2012. Long-term survival in infantile malignant autosomal recessive osteopetrosis secondary to homozygous p.Arg526Gln mutation in CLCN7. Am J Med Genet Part A 158A:909–916.

Abstract

Infantile malignant autosomal recessive osteopetrosis (ARO; OMIM 259700) has been reported to be associated with mutations in TCIRG1, CLCN7, or OSTM1. ARO caused by homozygous (or compound heterozygous) mutations in CLCN7, as described here, is usually diagnosed at birth or early in infancy due to generalized osteosclerosis and severe hematologic deficits. The maximal life expectancy of patients with ARO in the absence of bone marrow transplantation is thought to be 10 years. We report on a 25-year-old Thai man who is affected with ARO. Clinical features include proportionate short stature, vision impairment, esotropia, exophthalmos, mild hearing loss, and hepatosplenomegaly. Pancytopenia was present and the patient had frequent illnesses. Radiographs showed generalized osteosclerosis with almost no visible of bone marrow spaces. Dense maxilla and mandible with impacted and malformed teeth were observed. Multiple fractures were reported. He developed osteomyelitis of the mandible on four separate occasions, and partial mandibulectomy was performed. Molecular studies showed that there were no pathogenic mutations in TCIRG1. However, mutation analysis of CLCN7 revealed a homozygous missense mutation (p.Arg526Gln). This patient is, it appears, the longest lived individual with ARO ever reported. Evaluation of osteoclastogenesis in our patient demonstrated very large immature osteoclasts with a high number of nuclei. © 2012 Wiley Periodicals, Inc.

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