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Comparison of the clinical and cognitive features of genetically positive ALS patients from the largest tertiary center in Serbia

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Abstract

Discovering novel mutations in C9orf72, FUS, ANG, and TDP-43 genes in ALS patients arises necessities for better clinical characterizations of these subjects. The aim is to determine clinical and cognitive profile of genetically positive Serbian ALS patients. 241 ALS patients were included in the study (17 familiar and 224 apparently sporadic). The following genes were analyzed: SOD1, C9orf72, ANG, FUS, and TDP-43. An extensive battery of classic neuropsychological tests was used in 27 ALS patients (22 SOD1 positive and 5 SOD1 negative) and 82 healthy controls (HCs). Overall 37 (15.4%) of 241 ALS patients carried mutations in tested genes—among 17 familiar ALS patients 16 (94.1%) were positive and among 224 apparently sporadic 21 (9.4%) had causative mutation. Mutations in SOD1 gene were the most common, representing 27 (73.0%) of all genetically positive ALS patients. The main clinical characteristics of SOD1 positive patients were: spinal onset in lower extremities, common sphincter and sensitive disturbances, and dysexecutive syndrome. Within SOD1 positive patients, we noticed somewhat earlier onset in patients with A145G, sensory and sphincter disturbances were dominant in patients with L144F, while D90A patients had significant sensory involvement. SOD1 negative group consisted of ten (27.0%) patients (six C9orf72, two ANG, one TDP-43, and one patient baring triple FUS, C9orf72 expansion, and ANG variants). Bulbar involvement and more extensive neuropsychological impairment (including executive, visuospatial, and memory difficulties) were the main features of SOD1 negative cohort. Our results suggest that meaningful clinical suspicion of certain ALS genotype might be made based on thorough clinical evaluation of patients.

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Authors and Affiliations

  1. Neurology Clinic, Clinical Center of Serbia, School of Medicine, University in Belgrade, Dr Subotica 6, 11000, Belgrade, Serbia

    Ivan V. Marjanović, Ivana Basta, Dragana Lavrnić, Elka Stefanova & Zorica Stević

  2. Neurology Clinic, Clinical Center of Serbia, Belgrade, Serbia

    Biljana Selak-Djokić, Stojan Perić & Milena Janković

  3. Emergency Department, Clinic for Emergency Surgery, Clinical Center of Serbia, Belgrade, Serbia

    Vladimir Arsenijević

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  1. Ivan V. Marjanović
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  2. Biljana Selak-Djokić
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Correspondence to Ivan V. Marjanović.

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This study was approved by the Ethics Committee of the School of Medicine, University of Belgrade (Number 29/XI-6) and has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

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Marjanović, I.V., Selak-Djokić, B., Perić, S. et al. Comparison of the clinical and cognitive features of genetically positive ALS patients from the largest tertiary center in Serbia. J Neurol 264, 1091–1098 (2017). https://doi.org/10.1007/s00415-017-8495-y

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