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Novel mutation of TCIRG1 and clinical pictures of two infantile malignant osteopetrosis patients

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Abstract

Infantile malignant osteopetrosis (IMO) (OMIM 259700) is a lethal autosomal recessive disease. The underlying gene in most IMO patients is TCIRG1. This codes for the TCIRG1 protein involved in the cellular proton pump, which is highly expressed on surfaces of osteoclasts. We have characterized a family comprising two affected siblings born to healthy parents. The sister and her younger brother both presented classical X-ray images of IMO at 17 h and 16 weeks, respectively, after birth, and both died after the appearance of fever and flu-like symptoms months later. Radiographs revealed normal bone density in both parents. Mutation detection of the TCIRG1 gene was performed in the boy and the parents. The novel mutation c.242delC (p.Pro81ArgfsX85) and the known mutation c.1114C>T (p.Gln372X) were both identified in the boy. Both mutations are predicted to introduce premature stop codons, with deletion of 666 amino acids from the C terminus of the TCIRG1 protein of one allele and 459 from the other. Both mutations involve loss of part or the whole of the ATPase V0-complex domain of the protein. The father carries the c.242delC (p.Pro81ArgfsX85) mutation and the mother the c.1114C>T (p.Gln372X). Our findings provide new data for pre- and post-natal genetic diagnosis and identification of heterozygous carriers of the disease.

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Authors and Affiliations

  1. Department of Medical Genetics, Center for Genome Research, Zhongshan School of Medicine, Sun Yat-Sen University, 74 Zhongshan Road II, Guangzhou, 510080, People’s Republic of China

    Ping Yuan, Weijun Huang, Bin Hu & Yiming Wang

  2. Department of Paediatrics, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Zhihui Yue & Liangzhong Sun

  3. Department of Radiology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China

    Zhiyun Yang

  4. Department of Radiology, Guangzhou Women and Children’s Medical Center, Guangzhou, 510623, People’s Republic of China

    Yuelin Hu

  5. Department of Neurological Rehabilitation, Guangzhou Women and Children’s Medical Center, Guangzhou, 510120, People’s Republic of China

    Hua Xiao

  6. Department of Paediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou, 510623, People’s Republic of China

    Hui Shi

  7. Department of Paediatrics, The People’s Hospital of Yudu County, Ganzhou, 342300, People’s Republic of China

    Qing Zhou

Authors
  1. Ping Yuan
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  2. Zhihui Yue
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  3. Liangzhong Sun
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  4. Weijun Huang
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  5. Bin Hu
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  7. Yuelin Hu
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  8. Hua Xiao
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  9. Hui Shi
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  10. Qing Zhou
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  11. Yiming Wang
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Correspondence to Yiming Wang.

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Yuan, P., Yue, Z., Sun, L. et al. Novel mutation of TCIRG1 and clinical pictures of two infantile malignant osteopetrosis patients. J Bone Miner Metab 29, 251–256 (2011). https://doi.org/10.1007/s00774-010-0228-6

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  • DOI: https://doi.org/10.1007/s00774-010-0228-6

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