Muscular biopsy in myotonic dystrophy in the era of molecular genetics

Authors: Z. Lukáš 1;  I. Kroupová 1;  J. Bednařík 2;  M. Falk 3;  L. Fajkusová 4;  J. Sedláčková 4;  I. Valášková 5;  S. Voháňka 2
Authors‘ workplace: Ústav patologie LF MU a FN Brno 1;  Neurologická klinika LF MU a FN Brno 2;  Biofyzikální ústav AV ČR, Brno 3;  Centrum molekulární biologie a genové terapie hematoonkologické kliniky LF MU a FN Brno 4;  Oddělení klinické genetiky FN Brno 5
Published in: Cesk Slov Neurol N 2007; 70/103(4): 395-401
Category: Short Communication

Podpořeno grantem IGA MZ ČR NR 8052-3


The histopatological features of both so far defined types of myotonic dystrophy (DM1 and DM2) are very similar, the affected muscles show a typical pattern of changes. The examination of muscle biopsies in situ may also bring about revealing of expansions of CUG or CCUG repetitons in transcripts of the mutated DNA, the genetic basis of the diseases, which may be demonstreated by FISH (fluorescence in situ hybridization) as intranuclear focal accumulation of the transcript. In order to evaluate the importance of muscle biopsy including FISH at the time, when the diagnosis of DM is based on DNA analysis from blood lymphocytes, we analysed the results of histopathological examination of 34 patients, where the biopsy was indicated by clinical suspicion of myotonic dystrophy. The diagnosis was verified by mutation analysis of DNA for both DM1 and DM2. The examination was supplemented by FISH in 27 patients. The diagnosis of DM1 was confirmed in 13 patients, DM2 in 10 patients, the diagnosis of DM1 or DM2 was not confirmed in 11 patients. The biopsy brought about confirmation or precision-specification of the clinical diagnosis or suggested the diagnosis of DM in the majority of the patients. The bioptic findings in some patients with DM were atypical: in two cases there was inflammatory infiltration, in one case a picture resembling congenital myopathy. On the other hand, histopathological features of myotonic dystrophy were present in several biopsies where the diagnosis of DM was not confirmed. Focal accumulation of CUG/CCUG repeats in myonuclei was demonstrated by fluorescence in situ hybridization – in accordance with the DNA examination – in 23 patients, 13 with DM1 and 10 with DM2. Mutation analysis of the DNA isolated from blood leukocytes represent the method of choice if the diagnosis of DM is suspected. On the other hand, muscle biopsy may reveal histopathological features that may indicate subsequent molecular genetic examination of the patient if the results of the clinical examination are equivocal or atypical. FISH in the biopsy may reveal the intranuclear focal accumulation of the RNA transcripts in cells and tissues of the affected patiens and, in this way, to suggest a possible participation of them in the pathogenesis of the disease.

Key words:
myotonic dystrophy – biopsy – molecular genetics – diagnosis


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