Novel evidence of phenotypical variability in the hexanucleotide repeat expansion in chromosome 9

摘要: C9ORF72 repeat expansion is currently considered as a major genetic cause of amyotrophic lateral sclerosis (ALS) and, in particular, combined frontotemporal dementia-motor neuron disorder (FTD-MND) pedigrees. Studies large series patients have indicated that various phenotypic presentations may be observed even the same family. Here, we describe four carrying mutation with heterogeneous clinical presentation sharing rapid disease course. Cases #1 and #2 presented predominant semantic deficits, accompanied one patient by signs ALS. Case #3 showed phenotype compatible diagnosis behavioral variant FTD. #4 memory impairments, apathy, social withdrawal, had negative cerebrospinal fluid markers for Alzheimer's disease. Two positive familiar history MND dementia (at least first-degree family member affected). The two other were apparently sporadic cases. Our data provide further evidence heterogeneity phenotypes associated indicate its association fluent progressive aphasia phenotype. present findings confirm importance screening hexanucleotide chromosome 9 case not only familial, but also FTD, presence atypical cognitive disorders.