Document Detail

Whole-exome sequencing identifies mutations in the nucleoside transporter gene SLC29A3 in dysosteosclerosis, a form of osteopetrosis.
MedLine Citation:
PMID:  22875837     Owner:  NLM     Status:  MEDLINE    
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.
Philippe M Campeau; James T Lu; Gautam Sule; Ming-Ming Jiang; Yangjin Bae; Simran Madan; Wolfgang Högler; Nicholas J Shaw; Steven Mumm; Richard A Gibbs; Michael P Whyte; Brendan H Lee
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-08-08
Journal Detail:
Title:  Human molecular genetics     Volume:  21     ISSN:  1460-2083     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-26     Completed Date:  2013-03-26     Revised Date:  2013-12-05    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  4904-9     Citation Subset:  IM    
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MeSH Terms
Amino Acid Sequence
Child, Preschool
Molecular Sequence Data
Nucleoside Transport Proteins / genetics*
Osteopetrosis / genetics*,  radiography
Osteosclerosis / genetics*,  radiography
Sequence Alignment
Grant Support
F30 MH098571/MH/NIMH NIH HHS; P01 HD070394/HD/NICHD NIH HHS; P01 HD070394/HD/NICHD NIH HHS; P01 HD22657/HD/NICHD NIH HHS; R01 DK067145/DK/NIDDK NIH HHS; //Canadian Institutes of Health Research; //Howard Hughes Medical Institute
Reg. No./Substance:
0/Nucleoside Transport Proteins; 0/SLC29A3 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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