Characterization of a family with c9FTD/ALS associated with the GGGGCC repeat expansion in C9ORF72.
BACKGROUND
The hexanucleotide repeat in the chromosome 9 open reading frame 72 (C9ORF72) gene was recently discovered as the underlying genetic cause of many families with frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS) linked to chromosome 9 (c9FTD/ALS). We report the clinical, neuropsychologic, and neuroimaging findings of a family with the C9ORF72 mutation and clinical diagnoses bridging the FTD, parkinsonism, and ALS spectrum.


OBJECTIVE
To characterize the antemortem characteristics of a family with c9FTD/ALS associated with the GGGGCC repeat expansion in C9ORF72.


METHODS
Clinical series.


METHODS
Tertiary care academic medical center. PATIENTS The members of a family affected by the mutation with features of FTD and/or ALS.


METHODS
Clinical, neuropsychologic, and neuroimaging assessments.


RESULTS
All 3 examined subjects had the hexanucleotide expansion detected in C9ORF72. All had personality/behavioral changes early in the course of the disease. One case had levodopa-unresponsive parkinsonism, and 1 had ALS. Magnetic resonance imaging showed symmetric bilateral frontal, temporal, insular, and cingulate atrophy.


CONCLUSIONS
This report highlights the clinical and neuroimaging characteristics of a family with c9FTD/ALS. Further studies are needed to better understand the phenotypical variability and the cliniconeuroimaging-neuropathologic correlations.
Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Rodolfo
R
Savica
Anahita
A
Adeli
Prashanthi
P
Vemuri
David S
DS
Knopman
Mariely
M
Dejesus-Hernandez
Rosa
R
Rademakers
Julie A
JA
Fields
Jennifer
J
Whitwell
Clifford R
CR
Jack
Val
V
Lowe
Ronald C
RC
Petersen
Bradley F
BF
Boeve
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D000073885:C9orf72 Protein; D042622:DNA Repeat Expansion; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics* / Q000473:pathology / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010375:Pedigree; D011506:Proteins / Q000235:genetics*
D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins