Document Detail

Molecular genetic studies of DMT1 on 12q in French-Canadian restless legs syndrome patients and families.
MedLine Citation:
PMID:  17510944     Owner:  NLM     Status:  MEDLINE    
Converging evidence from clinical observations, brain imaging and pathological findings strongly indicate impaired brain iron regulation in restless legs syndrome (RLS). Animal models with mutation in (DMT1) divalent metal transporter 1 gene, an important brain iron transporter, demonstrate a similar iron deficiency profile as found in RLS brain. The human DMT1 gene, mapped to chromosome 12q near the RLS1 locus, qualifies as an excellent functional and possible positional candidate for RLS. DMT1 protein levels were assessed in lymphoblastoid cell lines from RLS patients and controls. Linkage analyses were carried out with markers flanking and within the DMT1 gene. Selected patient samples from RLS families with compatible linkage to the RLS1 locus on 12q were fully sequenced in both the coding regions and the long stretches of UTR sequences. Finally, selected sequence variants were further studied in case/control and family-based association tests. A clinical association of anemia and RLS was further confirmed in this study. There was no detectable difference in DMT1 protein levels between RLS patient lymphoblastoid cell lines and normal controls. Non-parametric linkage analyses failed to identify any significant linkage signals within the DMT1 gene region. Sequencing of selected patients did not detect any sequence variant(s) compatible with DMT1 harboring RLS causative mutation(s). Further studies did not find any association between ten SNPs, spanning the whole DMT1 gene region, and RLS affection status. Finally, two DMT1 intronic SNPs showed positive association with RLS in patients with a history of anemia, when compared to RLS patients without anemia.
Lan Xiong; Patrick Dion; Jacques Montplaisir; Anastasia Levchenko; Pascale Thibodeau; Liliane Karemera; Jean-Baptiste Rivière; Judith St-Onge; Claudia Gaspar; Marie-Pierre Dubé; Alex Desautels; Gustavo Turecki; Guy A Rouleau
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics     Volume:  144B     ISSN:  1552-4841     ISO Abbreviation:  Am. J. Med. Genet. B Neuropsychiatr. Genet.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-20     Completed Date:  2007-12-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  101235742     Medline TA:  Am J Med Genet B Neuropsychiatr Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  911-7     Citation Subset:  IM    
Copyright Information:
(c) 2007 Wiley-Liss, Inc.
Laboratoire d'étude des maladies du cerveau, Centre de recherche du CHUM, Hôpital Notre-Dame, Université de Montréal, 1560 rue Sherbrooke Est, Montréal, Québec, Canada.
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MeSH Terms
Case-Control Studies
Cation Transport Proteins / genetics*
Chromosomes, Human, Pair 12*
France / ethnology
Genetic Predisposition to Disease
Genetic Variation
Genome, Human
Molecular Biology
Polymorphism, Single Nucleotide
Restless Legs Syndrome / genetics*
Sequence Analysis, DNA
Reg. No./Substance:
0/Cation Transport Proteins; 0/solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2

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

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