title: Prevalence and characteristics of dystrophin defects in adult male patients with dilated cardiomyopathy.
abstract: OBJECTIVE
  To assess the prevalence of dystrophin defects in dilated cardiomyopathy (DCM) in male patients and to formulate investigation strategies for their identification.
  
  
  BACKGROUND
  Dystrophin defects presenting with predominant or exclusive cardiac involvement may be clinically indistinguishable from "idiopathic" DCM. Diagnosis may be missed, unless specifically investigated.
  
  
  METHODS
  Clinical and biochemical evaluation, right ventricular endomyocardial biopsy (EMB), light and electron microscopic and immunohistochemical studies of biopsy samples, six multiplex and two single polymerase chain reactions for 38 exons and automated sequencing of exon 9 and muscle promoter-exon 1 were undertaken in 201 consecutive male patients presenting with DCM, with (n = 14) and without (n = 187) increased serum creatine phosphokinase (sCPK).
  
  
  RESULTS
  Dystrophin defects were identified in 13 of the 201 patients (6.5%, age 16-50). Family history was positive in four patients. Serum CPK levels were increased in 11 of 13 patients. Light microscopy examination of EMB was uninformative; ultrastructural study showed multiple membrane defects. Dystrophin immunostain was abnormal. Eight patients, all older than 20, had deletions affecting midrod domain, normal or mildly increased CPK and better outcome than the five remaining cases all younger than 20, with more than five-fold increase of sCPK. Two of these latter had proximal and rod-domain deletions. Sisters of two patients were diagnosed as noncarriers with microsatellite analysis.
  
  
  CONCLUSIONS
  Although the overall prevalence of dystrophin defects in our consecutive DCM male series is low (6.5%), immunohistochemical and molecular studies are essential to identify protein and gene defects; screening studies are justified to define prevalence, clinical profile and genotype-phenotype correlation.
authors.affiliation: Pathology Department, IRCCS-Policlinico San Matteo, Pavia, Italy. e.arbustini@smatteo.pv.it
authors.forename: E
authors.initials: E
authors.lastname: Arbustini
authors.forename: M
authors.initials: M
authors.lastname: Diegoli
authors.forename: P
authors.initials: P
authors.lastname: Morbini
authors.forename: B
authors.initials: B
authors.lastname: Dal Bello
authors.forename: N
authors.initials: N
authors.lastname: Banchieri
authors.forename: A
authors.initials: A
authors.lastname: Pilotto
authors.forename: F
authors.initials: F
authors.lastname: Magani
authors.forename: M
authors.initials: M
authors.lastname: Grasso
authors.forename: J
authors.initials: J
authors.lastname: Narula
authors.forename: A
authors.initials: A
authors.lastname: Gavazzi
authors.forename: M
authors.initials: M
authors.lastname: Viganò
authors.forename: L
authors.initials: L
authors.lastname: Tavazzi
mesh_terms: D000293:Adolescent; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000473:pathology; D016189:Dystrophin / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D015995:Prevalence
chemical_list: D016189:Dystrophin