Abstract
Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, osteosclerosis, acro-osteolysis, frequent fractures, and skull deformities. Mutation in the gene encoding cathepsin K (CTSK), which is a lysosomal cysteine protease, has been found to be responsible for this disease. Here we reported a consanguineous Chinese family with 1 affected individual demonstrating autosomal recessive pycnodysostosis with recurrent kidney stone, a new clinical manifestation which has not been reported in patients of pycnodysostosis before. To identify the pathogenic mutation, we evaluated the patient clinically, biochemically, and radiographically. To screen for mutations in the CTSK gene of the patient and his family members, all of its exons and exon–intron junctions were PCR amplified from genomic DNA and sequenced. Sequence analysis of the patient’s CTSK gene revealed homozygosity for a missense mutation (c.746T>C) in exon 6, which leads to amino change (p.Ile249Thr) in the mature CTSK protein. This mutation was firstly reported by Michela Donnarumma and his colleagues in 2007 in a Spanish family. Our study strengthens the role of this particular mutation in the pathogenesis of pycnodysostosis.
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Acknowledgments
We appreciate our patient and their families for their participating in this study. This study was supported by a grant from the Ministry of Science and Technology of the People’s Republic of China (National Science and Technology Major Projects for “Major New Drugs Innovation and Development” 2008ZX09312-016), National Natural Science Foundation of China (No. 81070687 and 81170805), Beijing Natural Science Foundation (No. 7121012), Scientific Research Foundation of Beijing Medical Development (No. 2007-3029), and National Key Program of Clinical Science (WBYZ2011-873). All listed authors have each made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; participated in drafting the manuscript or revising it critically for content; and have approved the final version of the submitted manuscript. Dr. Xiang-Lan Huang, Dr. Xuan Qi, and Prof. Wei-Bo Xia accept responsibility for the integrity of the data analysis.
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The authors declare that there is no conflict of interest regarding the publication of this paper.
Human and Animal Rights and Informed Consent
Informed consents and approvals from the Department of Scientific Research at Peking Union Medical College Hospital (PUMCH), the local ethic committee, were obtained before the study.
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Xianglan Huang and Xuan Qi have contributed equally to this work and should be regarded as co-first authors.
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Huang, X., Qi, X., Li, M. et al. A Mutation in CTSK Gene in an Autosomal Recessive Pycnodysostosis Family of Chinese Origin. Calcif Tissue Int 96, 373–378 (2015). https://doi.org/10.1007/s00223-015-9963-y
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DOI: https://doi.org/10.1007/s00223-015-9963-y