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  • Perinatal/Neonatal Case Presentation
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Perinatal/Neonatal Case Presentation

Chloride Channel CICN7 Mutations in a Korean Patient with Infantile Malignant Osteopetrosis Initially Presenting with Neonatal Thrombocytopenia

Journal of Perinatology volume 24, pages 312–314 (2004)Cite this article

A Corrigendum to this article was published on 26 August 2004

Infantile malignant Osteopetrosis (Autosomal Recessive Osteopterosis, ARO, MIM 259700) is a genetically heterogenous autosomal recessive disorder of bone metabolism, which, if untreated, has a fatal outcome. Early death is common, with only 30% survival at 6 years of age.1,2,3 It is characterized by generalized osteosclerosis, secondary to bone marrow failure with anemia and thrombocytopenia with subsequent extramedullary hematopoiesis and impaired vision and hearing due to encroachment of nerve canals.1,2,3 Other presentations include failure to thrive and recurrent infections, both secondary to the underlying anemia and bone marrow involvement. A defect in macrophage killing of bacteria may account for recurrent and sometimes overwhelming infection. Hypocalcemic seizures,4 excessive bruising, nontraumatic fractures, abnormal craniofacial appearance (macrocephaly and frontal bossing) and snuffling because of disruption of nasal architecture are also less common complaints.3 Neurological involvement can range from mild developmental delay to generalized neurodegeneration, which may be associated with primary retinal degeneration.1

The exact incindence of autosomal recessive osteopetrosis is not known, but is estimated to be 1 in 200,000.5 It should be distinguished from the autosomal dominant adult disease (ADOI, MIM 607634 and ADOII, MIM 166600) and the carbonic anhydrase II deficiency, which is associated with renal tubular acidosis and cerebral calcification (MIM 259730). In recent decades, a number of intermediate forms associated with mild autosomal recessive inheritance (MIM 259710) and mild symptoms have been reported (MIM 259710).6 Recently, genetic and mutational analysis found several mutations in malignant osteopetroses. Especially two genes, ATP6i (TCIRG1) and ClCN7, have been identified to be associated with human ARO. ATP6i gene, encoding the a3 subunits of the vacuolar proton pump, which mediates the acidification of the bone/osteoclast interface, is responsible for about 58% of patients affected by ARO.2

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Authors and Affiliations

  1. Seoul National University College of Medicine, Seoul, Republic of Korea

    Youn-Jeong Shin MD, So Eun Park, MD MD, Ghyu Hong Shim MD, Jin A Lee MD, Ee Kyung Kim MD, Jun Dong Park MD, Beyong IL Kim MD, PhD & Jung Hwan Choi MD, PhD

  2. Istituto di Tecnologie Biomediche, CNR, Segrate, Milan, Italy

    Annalisa Frattini PhD

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Shin, YJ., Park, MD, S., Shim, G. et al. Chloride Channel CICN7 Mutations in a Korean Patient with Infantile Malignant Osteopetrosis Initially Presenting with Neonatal Thrombocytopenia. J Perinatol 24, 312–314 (2004). https://doi.org/10.1038/sj.jp.7211081

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