Phenotypic variability within the inclusion body spectrum of basophilic inclusion body disease and neuronal intermediate filament inclusion disease in frontotemporal lobar degenerations with FUS-positive inclusions.
Basophilic inclusion body disease and neuronal intermediate filament inclusion disease (NIFID) are rare diseases included among frontotemporal lobar degenerations with FUS-positive inclusions (FTLD-FUS). We report clinical and pathologic features of 2 new patients and reevaluate neuropathologic characteristics of 2 previously described cases, including an early-onset case of basophilic inclusion body disease (aged 38 years) with a 5-year disease course and abundant FUS-positive inclusion bodies and 3 NIFID cases. One NIFID case (aged 37 years) presented with early-onset psychiatric disturbances and rapidly progressive cognitive decline. Two NIFID cases had later onset (aged 64 years and 70 years) and complex neurologic deficits. Postmortem neuropathologic studies in late-onset NIFID cases disclosed α-internexin-positive "hyaline conglomerate"-type inclusions that were positive with 1 commercial anti-FUS antibody directed to residues 200 and 250, but these were negative to amino acids 90 and 220 of human FUS. Early-onset NIFID had similar inclusions that were positive with both commercial anti-FUS antibodies. Genetic testing performed on all cases revealed no FUS gene mutations. These findings indicate that phenotypic variability in NIFID, including clinical manifestations and particular neuropathologic findings, may be related to the age at onset and individual differences in the evolution of lesions.
Neurological Tissue Bank, Biobanc-Hospital Clínic-IDIBAPS, Barcelona, Spain. ellen.gelpi@gmail.com
Ellen
E
Gelpi
Albert
A
Lladó
Jordi
J
Clarimón
Maria Jesús
MJ
Rey
Rosa Maria
RM
Rivera
Mario
M
Ezquerra
Anna
A
Antonell
Judith
J
Navarro-Otano
Teresa
T
Ribalta
Gerard
G
Piñol-Ripoll
Anna
A
Pérez
Francesc
F
Valldeoriola
Isidre
I
Ferrer
D000328:Adult; D000368:Aged; D001491:Basophils / Q000473:pathology*; D004252:DNA Mutational Analysis; D005260:Female; D057174:Frontotemporal Lobar Degeneration / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D002479:Inclusion Bodies / Q000473:pathology*; D007382:Intermediate Filaments / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000473:pathology*; D010641:Phenotype; D011180:Postmortem Changes; D034702:RNA-Binding Protein FUS / Q000378:metabolism*
D034702:RNA-Binding Protein FUS