Heterozygotic gene expression in endomyocardial biopsies: a new diagnostic tool confirms the Duchenne carrier status.
Identification of the defective gene and the absent gene product dystrophin can substantiate the clinical evidence for manifesting X-linked Duchenne type muscular dystrophy (DMD). It is not always possible, however, to rule out definitely a clinically asymptomatic carrier status in question, since even in the proven carrier DNA analysis is often inconclusive, and multinucleated skeletal muscle fibers express a basically normal membrane dystrophin. To substantiate the value of endomyocardial biopsy as a new tool for detection of the DMD carrier status we examined an endomyocardial biopsy of a volunteer who met the clinical criteria of a DMD carrier. Dystrophin immunohistochemistry and western blot of her skeletal muscle biopsy were inconclusive, and polymerase chain reaction and cDNA analysis failed to locate directly the X-chromosomal defect. We observed a clearcut mosaic of dystrophin-positive and -negative mononucleated cardiac muscle cells, reflecting a heterozygote carrier status in her endomyocardial biopsy, whereas 20 controls were uniformely positive. The incidence of DMD (1:3000 males) and especially the 30% spontaneous mutation rate, still the major pitfall in DNA analysis, show the need for an additional diagnostic tool.
Schmidt-Achert
M
M
Friedrich-Baur-Institut bei der Medizinischen Klinik, Ludwig-Maximilians-Universität München.
Fischer
P
P
Müller-Felber
W
W
Mudra
H
H
Pongratz
D
D
D000328:Adult; D001706:Biopsy; D015153:Blotting, Western; D016189:Dystrophin / Q000032:analysis; D005260:Female; D015870:Gene Expression; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D007124:Immunoenzyme Techniques; D009136:Muscular Dystrophies / Q000235:genetics* / Q000473:pathology; D009206:Myocardium / Q000737:chemistry / Q000473:pathology*; D010375:Pedigree
D016189:Dystrophin