Résumé :
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Myotonic dystrophy type 2 (DM2) is caused by (CCTG)n repeat expansion in the first intron of ZNF9 gene, with the smallest reported disease causing expansion of 75 repeats. Repeat region consists of a complex motif (TG)12-26(TCTG)7-12(CCTG)3-9(G/TCTG)0-4(CCTG)4-15 of which only the uninterrupted (CCTG)n repeats have been suggested to cause DM2 phenotype. Here we report that in one patient with mild clinical phenotype of DM2 disease only 55 CCTG repeats were seen in DNA samples isolated from both peripheral blood leukocytes and muscle tissue. This small repeat expansion was not detected by chromogenic in situ hybridization from muscle sections, but was seen with a modified Southern technique and a PCR based method which amplifies the repeat region (RP-PCR, repeat primed). The repeat region was further analyzed by cloning and small-pool PCR to define the instability and the number of CCTG repeats in the complex motif. We could identify an instable expansion allele consisting of 55 CCTG repeats with no G/TCTG interruptions compatible with a disease causing small DM2 mutation. The patient has muscle weakness since age 50 years and early cataracts. Myotonia is seen neither clinically nor 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 finding of 55 CCTG repeats containing DM2 mutation suggests that even shorter than previously reported expansion of (CCTG)75 can cause DM2 disease. Further studies include haplotype analysis to assess whether this small expansion is of same founder origin as the general European DM2 mutation.
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