Adult XXXX with autosomal dominant transmission: a distinct entity caused by mutation in the glial fibrillary acid protein gene.

@entity1 @entity17 @entity538 @entity70589 @entity194 @entity26008 @entity4238 @entity8053 @entity25 @entity386
BACKGROUND: Infantile and juvenile forms of @entity26008 are well characterized and are caused by de novo mutations in the glial fibrillary acid protein ( @entity538 ) gene. In contrast, the adult form of the disease has been rarely described, and the etiology of this variant remains unknown. OBJECTIVE: To characterize the clinical phenotype and identify the gene causing an autosomal dominant form of adult @entity26008 . METHODS: We identified a large kindred segregating clinical features compatible with adult @entity26008 in an autosomal dominant fashion. A neurological examination was performed on all affected members of this family. Most of these @entity1 also underwent magnetic resonance imaging of the brain and a polysomnographic study. The diagnosis was confirmed pathologically in 2 individuals. We screened all coding regions of the @entity538 gene in affected individuals by means of direct sequencing and single-stranded conformational polymorphisms analysis. RESULTS: We found a novel @entity70589 mutation in @entity538 in all affected individuals. This mutation was not detected in more than 100 control subjects. Clinical and radiological features of affected individuals were clearly different from those of @entity1 with the infantile and juvenile forms of the disease. The most consistent finding was the presence of bulbar signs. In addition, @entity25 (mainly sleep @entity386 ), symptoms of @entity8053 , and @entity4238 were found in all affected individuals. In younger @entity1 , magnetic resonance imaging showed T2 signal abnormalities in the medulla compatible with an area of @entity17 . In contrast, in older @entity1 , we found marked @entity194 without signal abnormalities. None of the affected individuals exhibit signs of @entity17 . CONCLUSIONS: The present study is the first demonstration of a mutation in @entity538 that causes an autosomal dominant form of @entity26008 and establishes the existence of the adult variant. Clinical evaluation in individuals carrying mutation in the @entity538 gene allowed a better definition of this heterogeneous clinical syndrome and will help increase its recognition in neurological practice.
