Frontotemporal Dementia in a Brazilian Kindred With the C9orf72 Mutation

Figure 1. The UCSFBR1 kindred pedigree. Diagonal lines indicate deceased; arrowhead, proband; +, individuals who were tested for the C9orf72 mutation; ALS, amyotrophic lateral sclerosis; and bvFTD, behavioral variant frontotemporal dementia.

Figure 2. Parasagittal and axial T1-weighted 3-T brain magnetic resonance images. A, Patient III-1 has mild atrophy in the dorsal and posterior aspects of the brain. B, Patient II-4 has mild atrophy of the anterior temporal lobes, insula, and orbitofrontal region as well as dorsal atrophy.

Figure 3. Molecular genetic analyses of C9orf72 repeat expansions in the UCSFBR1 family. A, Fluorescent fragment-length analysis of a polymerase chain reaction fragment containing the GGGGCC repeat in C9orf72 in 4 patients (II-1, III-1, II-2, and II-4) and an unaffected spouse (II-0). A lack of transmission from the affected parent (II-1) to the affected offspring (III-1) is seen. Numbers under the peaks indicate the number of GGGGCC hexanucleotide repeats. B, Polymerase chain reaction products of repeat-primed polymerase chain reactions separated on an ABI3730 DNA Analyzer (Applied Biosystems) and visualized by GeneMapper software (Applied Biosystems). Electropherograms are zoomed to 2000 relative fluorescence units to show stutter amplification. Results from an expanded repeat carrier (II-1) and a healthy control are shown. C, Southern blotting of 3 expanded repeat carriers and an unaffected spouse using genomic DNA extracted from blood. Patients with expanded repeats (II-1, III-1, and II-2) show additional alleles ranging from 5 to 23 kilobases, while the unaffected spouse (II-0) shows only the expected approximately 2.3-kilobase wild-type allele.