Document Detail


A non-DM1, non-DM2 multisystem myotonic disorder with frontotemporal dementia: phenotype and suggestive mapping of the DM3 locus to chromosome 15q21-24.
MedLine Citation:
PMID:  15215218     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The majority of proximal myotonic myopathy syndromes reported so far have been related to the myotonic dystrophy (DM) type 2 (DM2) mutation, an expanded (CCTG)n repeat in the ZNF9 gene. Here, we describe the phenotype and the histological features in muscle and brain of the first large pedigree with a non-myotonic dystrophy type 1 (DM1) non-DM2 multisystem myotonic disorder associated with severe frontotemporal dementia. Thirty individuals from three generations underwent detailed neurological, neuropsychological, electrophysiological, brain imaging and molecular analyses. Ten of them had proximal muscle weakness at onset, clinical/electrical myotonia and DM-type cataracts. The mean age at onset was 46.7 +/- 12.6 years (range: 32-69). Dementia was observed later in the course of the disease. On muscle biopsies, rare nuclear clumps, rimmed vacuoles and small angulated type 1 and type 2 fibres were seen early in the disease. They were replaced by fibrous adipose tissue at later stages. Immunohistochemical analysis of myosin heavy chain isoforms showed no selective fibre type atrophy-both type 1 and type 2 fibres being affected. Cortical atrophy without white matter lesions was seen on brain MRI. A brain single photon emission computed tomography (SPECT) study revealed marked frontotemporal hypoperfusion. Post-mortem examination of the brains of two patients showing prominent frontotemporal spongiosis, neuronal loss and rare neuronal and glial tau inclusions suggested frontotemporal dementia. Western blot analyses of the tau protein showed a triplet of isoforms (60, 64 and 69 kDa) in neocortical areas, and a doublet (64 and 69 kDa) in subcortical areas that distinguish our myotonic disorder from other's myotonic dystrophies. Molecular analyses failed to detect a repeat expansion in the DMPK and ZNF9 genes excluding both DM1 and DM2, whereas a genome-wide linkage analysis strongly suggested a linkage to chromosome 15q21-24. This previously unreported multisystem myotonic disorder including findings resembling DM1, DM2 and frontotemporal dementia provides further evidence of the clinical and genetic heterogeneity of the myotonic dystrophies. We propose to designate this disease myotonic dystrophy type 3, DM3.
Authors:
Isabelle Le Ber; Maria Martinez; Dominique Campion; Annie Laquerrière; Christine Bétard; Guillaume Bassez; Carol Girard; Pascale Saugier-Veber; Gregory Raux; Nicolas Sergeant; Patrick Magnier; Thierry Maisonobe; Bruno Eymard; Charles Duyckaerts; André Delacourte; Thierry Frebourg; Didier Hannequin
Related Documents :
7988088 - Limb girdle muscular dystrophy: reappraisal of a rejected entity.
1674498 - Physical and genetic mapping of a novel chromosome 19 ercc1 marker showing close linkag...
9811228 - Penetration of natural prostaglandins and their ester prodrugs and analogs across human...
11281448 - Hybrids monosomal for human chromosome 5 reveal the presence of a spinal muscular atrop...
8500788 - Hla-a/b haplotye frequencies among u.s. hispanic and african-american populations.
7095658 - Cytogenetic study of a cercopithecus pogonias grayi x cercopithecus mona mona hybrid.
Publication Detail:
Type:  Journal Article     Date:  2004-06-23
Journal Detail:
Title:  Brain : a journal of neurology     Volume:  127     ISSN:  1460-2156     ISO Abbreviation:  Brain     Publication Date:  2004 Sep 
Date Detail:
Created Date:  2004-08-23     Completed Date:  2004-10-15     Revised Date:  2008-05-13    
Medline Journal Info:
Nlm Unique ID:  0372537     Medline TA:  Brain     Country:  England    
Other Details:
Languages:  eng     Pagination:  1979-92     Citation Subset:  AIM; IM    
Affiliation:
Département de Neurologie, Centre Hospitalo-Universitaire Charles Nicolle, Rouen, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adult
Age of Onset
Aged
Chromosome Mapping / methods
Chromosomes, Human, Pair 15 / genetics*
Dementia / complications,  genetics*,  pathology
Female
Humans
Linkage (Genetics) / genetics
Magnetic Resonance Imaging
Male
Middle Aged
Muscle Weakness / etiology,  genetics,  pathology
Muscle, Skeletal / pathology
Myosin Heavy Chains / analysis
Myotonic Disorders / complications,  genetics*,  pathology
Pedigree
Phenotype
RNA-Binding Proteins / genetics
Sex Ratio
tau Proteins / analysis
Chemical
Reg. No./Substance:
0/CNBP protein, human; 0/Myosin Heavy Chains; 0/RNA-Binding Proteins; 0/tau Proteins

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


Previous Document:  A prospective study demonstrates an association between JC virus-specific cytotoxic T lymphocytes an...
Next Document:  Temporal lobectomy: long-term seizure outcome, late recurrence and risks for seizure recurrence.