Document Detail

X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus.
MedLine Citation:
PMID:  8504498     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: X-linked cardiomyopathy (XLCM) is a rapidly progressive primary myocardial disorder presenting in teenage males as congestive heart failure. Manifesting female carriers have later onset (fifth decade) and slower progression. The purpose of this study was to localize the XLCM gene locus in two families using molecular genetic techniques. METHODS AND RESULTS: Linkage analysis using 60 X-chromosome-specific DNA markers was performed in a previously reported large XLCM pedigree and a smaller new pedigree. Two-point and multipoint linkage was calculated using the LINKAGE computer program package. Deletion analysis included multiplex polymerase chain reaction (PCR). Dystrophin protein was evaluated by Western blotting with N-terminal and C-terminal dystrophin antibody. Linkage of XLCM to the centromeric portion of the dystrophin or Duchenne muscular dystrophy (DMD) locus at Xp21 was demonstrated with combined maximum logarithm of the scores of +4.33, theta = 0 with probe XJ1.1 (DXS206) using two-point linkage and +4.81 at XJ1.1 with multipoint linkage analysis. LOD scores calculated using other proximal DMD genomic and cDNA probes and polymerase chain reaction polymorphisms supported linkage. No deletions were observed. Abnormalities of cardiac dystrophin were shown by Western blotting with N-terminal dystrophin antibody, whereas skeletal muscle dystrophin was normal, suggesting primary involvement of the DMD gene with preferential involvement of cardiac muscle. CONCLUSIONS: XLCM is due to an abnormality within the centromeric half of the dystrophin genomic region in heart. This abnormality could be due to 1) a point mutation in the 5' region of the DMD coding sequence preferentially affecting cardiac function, 2) a cardiac-specific promoter mutation that alters expression in this tissue, 3) splicing abnormalities, resulting in an abnormal cardiac protein, or 4) deletion mutations undetectable by Southern and multiplex polymerase chain reaction analysis.
J A Towbin; J F Hejtmancik; P Brink; B Gelb; X M Zhu; J S Chamberlain; E R McCabe; M Swift
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Circulation     Volume:  87     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:  1993 Jun 
Date Detail:
Created Date:  1993-07-02     Completed Date:  1993-07-02     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1854-65     Citation Subset:  AIM; IM    
Baylor College of Medicine, Department of Pediatrics, Houston, TX 77030.
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MeSH Terms
Blotting, Western
Cardiomyopathy, Dilated / genetics*
Chromosome Mapping
DNA Probes
Dystrophin / genetics*
Linkage (Genetics)*
Lod Score
Middle Aged
Muscular Dystrophies / genetics*
Polymerase Chain Reaction
X Chromosome*
Grant Support
Reg. No./Substance:
0/DNA Probes; 0/Dystrophin

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