title: Long-term survival in infantile malignant autosomal recessive osteopetrosis secondary to homozygous p.Arg526Gln mutation in CLCN7.
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.
authors.affiliation: Faculty of Dentistry, Division of Pediatric Dentistry, Department of Orthodontics and Pediatric Dentistry, Craniofacial Genetics Laboratory, Chiang Mai University, DENTALAND CLINIC, Chiang Mai, Thailand. dentaland17@gmail.com
authors.forename: Piranit Nik
authors.initials: PN
authors.lastname: Kantaputra
authors.forename: Saranya
authors.initials: S
authors.lastname: Thawanaphong
authors.forename: Witchapong
authors.initials: W
authors.lastname: Issarangporn
authors.forename: Phennapha
authors.initials: P
authors.lastname: Klangsinsirikul
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohazama
authors.forename: Paul
authors.initials: P
authors.lastname: Sharpe
authors.forename: Chayarop
authors.initials: C
authors.lastname: Supanchart
mesh_terms: D000328:Adult; D018118:Chloride Channels / Q000235:genetics*; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D009154:Mutation; D020125:Mutation, Missense; D010010:Osteoclasts / Q000473:pathology*; D010022:Osteopetrosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics
chemical_list: C097540:CLCN7 protein, human; D018118:Chloride Channels; C472421:TCIRG1 protein, human; D025262:Vacuolar Proton-Translocating ATPases