Mutated CTSF in adult-onset neuronal ceroid lipofuscinosis and FTD
Related Experiment Video
Updated: Mar 14, 2026
Real-Time Fluorescent Measurement of Synaptic Functions in Models of Amyotrophic Lateral Sclerosis
Published on: July 16, 2021
Julie van der Zee1, Peter Mariën1, Roeland Crols1
1Neurodegenerative Brain Diseases Group (J.v.d.Z., S.V.M., L.D., F.P., A.S., C.V.B.), Department of Molecular Genetics, VIB, Antwerp; Institute Born-Bunge (J.v.d.Z., S.V.M., L.D., F.P., S.E., C.C.-D.G., A.S., P.C., J.-J.M., C.V.B.), CLIPS, Computational Linguistics and Psycholinguistics (J. Verhoeven), University of Antwerp; Department of Neurology and Memory Clinic (P.M., R.C., S.V.M., S.E.), ZNA Middelheim and Hoge Beuken, Antwerp; Clinical and Experimental Neurolinguistics (P.M., T.D.), Vrije Universiteit Brussel, Belgium; Department of Language and Communication Science (J. Verhoeven), City University, London, UK; Department of Neurology (A.S.), University Hospital Ghent and University of Ghent; Department of Neurology (S.V.M., P.C.), Antwerp University Hospital; and Department of Neurology (J. Versijpt), University Hospital Brussels, Belgium.
Objective:
To investigate the molecular basis of a Belgian family with autosomal recessive adult-onset neuronal ceroid lipofuscinosis (ANCL or Kufs disease [KD]) with pronounced frontal lobe involvement and to expand the findings to a cohort of unrelated Belgian patients with frontotemporal dementia (FTD).
Methods:
Genetic screening in the ANCL family and FTD cohort (n = 461) was performed using exome sequencing and targeted massive parallel resequencing.
Results:
We identified a homozygous mutation (p.Ile404Thr) in the Cathepsin F (CTSF) gene cosegregating in the ANCL family. No other mutations were found that could explain the disease in this family. All 4 affected sibs developed motor symptoms and early-onset dementia with prominent frontal features. Two of them evolved to akinetic mutism. Disease presentation showed marked phenotypic variation with the onset ranging from 26 to 50 years. Myoclonic epilepsy in one of the sibs was suggestive for KD type A, while epilepsy was not present in the other sibs who presented with clinical features of KD type B. In a Belgian cohort of unrelated patients with FTD, the same heterozygous p.Arg245His mutation was identified in 2 patients who shared a common haplotype.
Conclusions:
A homozygous CTSF mutation was identified in a recessive ANCL pedigree. In contrast to the previous associations of CTSF with KD type B, our findings suggest that CTSF genetic testing should also be considered in patients with KD type A as well as in early-onset dementia with prominent frontal lobe and motor symptoms.
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:39Mutations
01:22Lysosomal Hydrolases
03:03Amyloid Fibrils
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...