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CLINICAL STUDIES

Prevalence and characteristics of dystrophin defects in adult male patients with dilated cardiomyopathy

Eloisa Arbustini, MD^*, Marta Diegoli, BD^*, Patrizia Morbini, MD^*, Barbara Dal Bello, MD^*, Nadia Banchieri, BD^*, Andrea Pilotto, TD^*, Filippo Magani, TD^*, Maurizia Grasso, PhD, Jagat Narula, MD, Antonello Gavazzi, MD, Mario Viganò, MD^|| and Luigi Tavazzi, MD

^* Pathology Department, IRCCS-Policlinico San Matteo, Pavia, Italy
Cardiology Department, IRCCS-Policlinico San Matteo, Pavia, Italy
^|| Cardiac Surgery Department Departments, IRCCS-Policlinico San Matteo, Pavia, Italy
Transplantation Experimental Laboratory, IRCCS-Policlinico San Matteo, Pavia, Italy
Allegheny University of Health Science, Philadelphia, Pennsylvania, USA

Manuscript received August 10, 1999; revised manuscript received December 30, 1999, accepted February 21, 2000.

Reprint requests and correspondence: Dr. Eloisa Arbustini, Istituto di Anatomia Patologica, Viale Forlanini 16, 27100 Pavia, Italy
e.arbustini{at}smatteo.pv.it

OBJECTIVES

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.

Abbreviations and Acronyms   BMD = Becker muscular dystrophy   DAG = dystrophin-associated glycoprotein   DCM = dilated cardiomyopathy   ECG = electrocardiography   EMB = endomyocardial biopsy   LGMD = limb-girdle muscular dystrophy   MB = cardiac isoform   MM = muscle isoform   PCR = polymerase chain reaction   RT = reverse transcriptase   sCPK = serum creatine phosphokinase   STR = single tandem repeats

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