Résumé :
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Myotonic dystrophy type 2 (DM2) is caused by a (CCTG)n repeat expansion in the first intron of ZNF9 gene. The smallest reported expansion in leucocyte DNA with clinical phenotype consists of (CCTG)75 repeats. The repeat region is complex with both dinucleotide and tetranucleotide motifs: (TG)12-26(TCTG)7-12(CCTG)3- 9(G/TCTG)0-4(CCTG)4-15 and only the uninterrupted (CCTG)n repeats are suggested to cause the DM2 phenotype. Here we report that in three brothers in a Finnish family a repeat expansion of (CCTG)55 was seen. The proband had mild proximal lower limb muscle weakness, myalgic pains and stiffness of muscles and early cataract changes, but no myotonia either clinically or on EMG. Muscle biopsy shows findings characteristic of DM2 with highly atrophic type 2 fibers, nuclear clump fibers and increased number of internal nuclei. The proband was referred to DM2 molecular diagnostics because of the muscle pathology finding, and only one allele was amplified by PCR over the region. However, the short repeat was not detectable by chromogenic or fluorescent in situ hybridization (CISH or FISH) from muscle sections. With a modified southern blot technique and a PCR based method amplifying the repeat region (RP-PCR, repeat-primed) the short expansion could be seen. The sequencing of the repeat region revealed 55 CCTG repeats with no interruptions and instability of the repeat region was verified by small-pool PCR. Genotyping the region around the DM2 mutation showed a haplotype distinct from the haplotype previously found in Finnish DM2 patients. The index patient has two brothers with the same mutation and mild symptoms. Because of the lack of myotonia and ribonuclear foci in CISH and FISH the mechanism and also the clinical phenotype are different from the classic DM2 disease, and the myotonic dystrophy term cannot be applied to this different disease even if it is linked to the same genetic abnormality.
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