Genotype-phenotype correlation in Tunisian patients with Amyotrophic Lateral Sclerosis.

Journal: Neurobiology of aging

Volume: 120

Issue: 

Year of Publication: 2022

Affiliated Institutions:  Neurology Department, LRSP, Razi Universitary Hospital, Tunis, Tunisia; Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia; Clinical Investigation Center (CIC) "Neurosciences and Mental Health", Razi Universitary Hospital, Tunis, Tunisia. Neurology Department, LRSP, Razi Universitary Hospital, Tunis, Tunisia; Clinical Investigation Center (CIC) "Neurosciences and Mental Health", Razi Universitary Hospital, Tunis, Tunisia. Istituto Auxologico Italiano, IRCCS, Department of Neurology and Laboratory of Neuroscience, Milan, Italy. Istituto Auxologico Italiano, IRCCS, Department of Neurology and Laboratory of Neuroscience, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy. Istituto Auxologico Italiano, IRCCS, Department of Neurology and Laboratory of Neuroscience, Milan, Italy; Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano, Segrate, Milan, Italy. Istituto Auxologico Italiano, IRCCS, Department of Neurology and Laboratory of Neuroscience, Milan, Italy; Department of Pathophysiology and Transplantation, "Dino Ferrari" Center, Università degli Studi di Milano, Milan, Italy; "Aldo Ravelli" Center for Neurotechnology and Experimental Brain Therapeutics, Università degli Studi di Milano, Milan, Italy. Neurology Department, LRSP, Razi Universitary Hospital, Tunis, Tunisia; Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia; Clinical Investigation Center (CIC) "Neurosciences and Mental Health", Razi Universitary Hospital, Tunis, Tunisia. Electronic address: riadh.gouider@gnet.tn.

Abstract summary 

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease. To date, mutations in more than 30 genes have been linked to familial ALS forms. However, no mutational screenings have been reported in African populations so far. We aimed to investigate the presence of rare genetic variants in the 4 most common ALS causative genes among a Tunisian cohort. Patients were screened for mutations in SOD1 (exons 1-5), TARDBP (exon 6), FUS (exons 5, 6, 13/14, and 15). Juvenile ALS (JALS) patients were screened also for ALS2 (exons 3, 10, 28). Analysis of C9ORF72 was conducted by fluorescent amplicon-length analysis and repeat-primed PCR. We analyzed 197 Tunisian ALS patients, including 11 familial forms (fALS) with 17 ALS cases, 167 sporadic (sALS) and 13 JALS cases. The pathogenic variant TARDBP p.G294A mutation was reported among 18 patients. Repeat expansion in C9orf72 was recorded in 9 patients. Interestingly, 2 unrelated patients carried a double mutation in both C9orf72 and TARDBP genes. Finally, the p.Asp91Val mutation in SOD1 was identified among 4 cases in homozygous state including 3 sALS and 1 familial JALS with recessive inheritance. No pathogenic variants in FUS were identified, nor ALS2 variants in JALS cases. In our Tunisian cohort the most frequently mutated gene is TARDBP (9.4%), followed by C9orf72 (3.9%) and SOD1 (2.1%). Our study broadens the mutational spectrum in patients with ALS and defines for the first time the mutational frequency of the main ALS genes in patients of African ethnicity.

Authors & Co-authors:  Kacem Imen I Sghaier Ikram I Peverelli Silvia S Souissi Emira E Ticozzi Nicola N Gharbi Alya A Ratti Antonia A Berrechid Amina Gargouri AG Silani Vincenzo V Gouider Riadh R

Study Outcome 

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Citations : 
Authors :  10
Identifiers
Doi : 10.1016/j.neurobiolaging.2022.08.002
SSN : 1558-1497
Study Population
Male,Female
Mesh Terms
Humans
Other Terms
Amyotrophic Lateral Sclerosis (ALS);Genetics;Phenotype;TARDBP;Tunisia-Africa
Study Design
Cohort Study,Cross Sectional Study
Study Approach
Country of Study
Tunisia
Publication Country
United States