Myotonic dystrophies are genetic diseases with a dominant pattern of inheritance. Both DM1 and DM2 show abnormal repeating patterns in the DNA. Examination of DM biopsies reveals ribonuclear inclusions (RIs; abnormal RNAs that contain the repeating sequences) that accumulate in nuclei of the affected cells. Giovanni Meola, MD, Professor and Chair of Neurology, San Donato Polyclinical Institute, San Donato Milanese, Milan, Italy, reported this study that could lead to a differential diagnostic procedure for DM1 and DM2, based on differences between RIs in the affected muscle cells.

The study enrolled patients diagnosed with DM2 (n = 17), or with DM1 (n = 5), and a control group consisting of patients with other muscular disorders. In DM1, the DMPK gene on chromosome 19 is affected, including multiple CTG repeats in a region that is not translated into protein. In DM2, the ZNF9 gene on chromosome 3 contains multiple CCTG repeats in another noncoding region. Muscle biopsies were diagnosed biochemically using a specific (CAGG)₅ probe. This probe consists of 5 trinucleotide repeats of a base sequence complementary to the CCTG repeats that define DM2. The DM2 probe does not bind to the CTG repeats that characterise DM1 (their complementary sequence would be CAGCAG, the authors noted).

The authors describe results obtained with FISH using the specific (CAGG)₅ probe: "Ribonuclear inclusions were present in all 17 genetically confirmed DM2 subjects examined, and absent in all patients affected by DM1 (n = 5) or by other muscular disease[s] used as control (n = 17)." The authors note that this technique "might be a specific method to distinguish between DM1 and DM2 pathology."

A second facet of the study localised muscleblind-like protein (MBNL1), an RNA-binding protein in the nuclei of muscle cells. The researchers identified MBNL1 in muscle tissue from patients with DM1 (n = 7), patients with DM2 (n = 9), patients with non-DM1/DM2 dystrophies (n = 3), patients with channelopathies (n = 7), and normal controls (n = 5). MBNL1 was homogeneously distributed throughout the nuclei, except in muscle sections from the DM patients. In DM1 and DM2 patients, MBNL1 was located in highly concentrated foci.

An additional immunofluorescence study of muscle biopsies from DM1 (n = 7) and DM2 (n = 8) patients showed that the nuclear distribution of MBNL1 coincides precisely with the RI distribution.

Drawing together all of these findings, the authors conclude that: "MBNL1 could represent a histopathological marker of the DMs."


[Presentation title: Muscleblind-Like Protein (MBNL1) as Marker of Molecular Pathology for Myotonic Dystrophies. Abstract 57]

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