PT  - JOURNAL ARTICLE
AU  - Julie van der Zee
AU  - Peter Mariën
AU  - Roeland Crols
AU  - Sara Van Mossevelde
AU  - Lubina Dillen
AU  - Federica Perrone
AU  - Sebastiaan Engelborghs
AU  - Jo Verhoeven
AU  - Tine D'aes
AU  - Chantal Ceuterick-De Groote
AU  - Anne Sieben
AU  - Jan Versijpt
AU  - Patrick Cras
AU  - Jean-Jacques Martin
AU  - Christine Van Broeckhoven
TI  - Mutated <em>CTSF</em> in adult-onset neuronal ceroid lipofuscinosis and FTD
AID  - 10.1212/NXG.0000000000000102
DP  - 2016 Oct 01
TA  - Neurology Genetics
PG  - e102
VI  - 2
IP  - 5
4099  - http://ng.neurology.org/content/2/5/e102.short
4100  - http://ng.neurology.org/content/2/5/e102.full
SO  - Neurol Genet2016 Oct 01; 2
AB  - 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.ANCL=adult-onset neuronal ceroid lipofuscinosis; bv=behavioral variant; CTSF=cathepsin F; FTD=frontotemporal dementia; KD=Kufs disease; NCL=neuronal ceroid lipofuscinosis; PSP=progressive supranuclear palsy; STR=short tandem repeat