Novel XXXX mutation and no molecular evidence of anticipation in a family with cerebral and spinal cavernous malformations.

@entity1 @entity71500 @entity71501 @entity548 @entity1269 @entity16 @entity14826 @entity1504 @entity600 @entity3207 @entity5380 @entity29555 @entity3541 @entity11401
BACKGROUND: @entity5380 ( @entity5380 ) are @entity1504 which can result in a variety of @entity16 . @entity29555 is inherited as an autosomal-dominant trait. There is one study in the literature which reports statistical evidence for anticipation in familial @entity5380 . METHODS: We reevaluated the clinical course of the disease and performed molecular analyses in a previously described three-generation @entity5380 family with apparent anticipation. RESULTS: Disease started at a younger age in each generation, strongly suggesting anticipation. The @entity1 in generation I showed no clinical symptoms by the age of 68, whereas his son became wheelchair-bound at the age of 43 due to an intramedullary cavernous @entity600 at the thoracolumbar transition of the spinal cord. The @entity1 in generation III had a pons @entity548 at the age of 11 due to a large brainstem cavernoma. The @entity548 caused @entity3541 and @entity1269 , persisting as @entity11401 . Sequencing of @entity14826 identified a novel frameshift mutation in exon 15 ( @entity71500 or @entity71501 ) which cosegregated with the phenotype. Flow-FISH analysis of granulocyte and lymphocyte telomere length showed that telomeres were longest in the youngest affected family member. CONCLUSIONS: We could not find any evidence for either of the two currently known molecular mechanisms for genetic anticipation (i.e., expansion of repetitive DNA elements or progressive @entity3207 ) in this family. However, the family presented here raises the important question whether surveillance of @entity5380 families with gradient-echo MRI should not only include the cerebrum, but the spinal cord as well.
