Whole-exome sequencing identifies mutations in the nucleoside transporter gene SLC29A3 in dysosteosclerosis, a form of osteopetrosis
| Autor: | James T. Lu, Steven Mumm, Michael P. Whyte, Richard A. Gibbs, Yangjin Bae, Ming-Ming Jiang, Brendan Lee, Philippe M. Campeau, Simran Madan, Nicholas Shaw, Gautam Sule, Wolfgang Högler |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Molecular Sequence Data
Nucleoside Transport Proteins Nucleoside transporter Compound heterozygosity medicine.disease_cause Osteosclerosis Consanguinity Mice Osteoclast Genetics medicine Animals Humans Exome Amino Acid Sequence Molecular Biology Genetics (clinical) Exome sequencing Mutation biology Infant Osteopetrosis General Medicine Articles medicine.disease Radiography medicine.anatomical_structure Child Preschool Cancer research biology.protein Female Sequence Alignment |
| Popis: | Dysosteosclerosis (DSS) is the form of osteopetrosis distinguished by the presence of skin findings such as red-violet macular atrophy, platyspondyly and metaphyseal osteosclerosis with relative radiolucency of widened diaphyses. At the histopathological level, there is a paucity of osteoclasts when the disease presents. In two patients with DSS, we identified homozygous or compound heterozygous missense mutations in SLC29A3 by whole-exome sequencing. This gene encodes a nucleoside transporter, mutations in which cause histiocytosis-lymphadenopathy plus syndrome, a group of conditions with little or no skeletal involvement. This transporter is essential for lysosomal function in mice. We demonstrate the expression of Slc29a3 in mouse osteoclasts in vivo. In monocytes from patients with DSS, we observed reduced osteoclast differentiation and function (demineralization of calcium surface). Our report highlights the pleomorphic consequences of dysfunction of this nucleoside transporter, and importantly suggests a new mechanism for the control of osteoclast differentiation and function. |
| Databáze: | OpenAIRE |
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