| Popis: |
This chapter discusses clinical and genetic features of myotonic dystrophy type 2 (DM2). DM2 possesses several unique genetic features: it is the only identified tetranucleotide repeat disorder; DM2 expansions are larger than any other identified repeat expansion, exceeding 11,000 repeats with a mean of 5000 repeats; the degree of somatic mosaicism is unparalleled, with most subjects having dramatic heterogeneity of repeat length in blood; expansion length can increase over time, in one instance growing by 2 kb over 3 years; there is no discemable correlation between repeat length and disease severity. The size and somatic mosaicism have complicated genetic testing, but the currently available set of a PCR-based repeat assay and Southern analysis is reliable, sensitive, and specific. However, the lack of correlation between repeat length and severity suggests that the pathogenic mechanism is saturable, with no further increase in pathogenicity as repeat lengths expand beyond a size with maximal effect; this ceiling effect is further reflected by the fact that individuals homozygous for DM2 expansions are clinically indistinguishable from those with only one expanded allele. |
