Replication study of MATR3 in familial and sporadic amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder characterized by an extensive loss of motor neurons in the primary motor cortex, brainstem, and spinal cord. Genetic studies report a high heritability of ALS. Recently, whole-exome sequencing analysis of familial ALS (FALS) patients allowed the identification of missense variations within the MATR3 gene. MATR3 was previously associated to distal myopathy 2 and encodes for a nuclear matrix and DNA/RNA binding protein that has been shown to interact with TDP43 in an RNA-dependent manner. Here, we assessed the MATR3 mutation frequency in French-Canadian ALS and control individuals (nFALS = 83, sporadic ALS [nSALS] = 164, and ncontrols = 162) and showed that MATR3 mutations were found in 0%, 1.8%, and 0% of FALS, SALS, and controls, respectively. Interestingly, among the mutations identified in SALS, the splicing mutation c.48+1G>T was found to result in the insertion of 24 amino acids in MATR3 protein. These findings further support the role of MATR3 in ALS, and more studies are needed to shed more light on MATR3 proteinopathy.
Department of Human Genetics, McGill University, Montreal, Québec, Canada; Montreal Neurological Institute and Hospital, McGill University, Montreal, Québec, Canada.
Claire S
CS
Leblond
Department of Human Genetics, McGill University, Montreal, Québec, Canada; Montreal Neurological Institute and Hospital, McGill University, Montreal, Québec, Canada.
Ziv
Z
Gan-Or
Montreal Neurological Institute and Hospital, McGill University, Montreal, Québec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada.
Dan
D
Spiegelman
Montreal Neurological Institute and Hospital, McGill University, Montreal, Québec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada.
Sandra B
SB
Laurent
Montreal Neurological Institute and Hospital, McGill University, Montreal, Québec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada.
Anna
A
Szuto
Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Québec, Canada.
Alan
A
Hodgkinson
Montreal Neurological Institute and Hospital, McGill University, Montreal, Québec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada.
Alexandre
A
Dionne-Laporte
Department of Medicine, University of Laval, Quebec City, Québec, Canada.
Pierre
P
Provencher
Faculty of Medicine, Department of Neurosciences, University of Lisbon, Hospital de Santa Maria-CHLN, Lisbon, Portugal.
Mamede
M
de Carvalho
Medical Genetics, Department of Medical Sciences, University of Cagliari, Cagliari, Italy.
Sandro
S
Orrù
Department of Medicine, University of Laval, Quebec City, Québec, Canada; Neuromuscular and Neurogenetic Disease Clinic, Centre Hospitalier Universitaire de Québec, Quebec City, Québec, Canada.
Denis
D
Brunet
Department of Medicine, University of Laval, Quebec City, Québec, Canada; Neuromuscular and Neurogenetic Disease Clinic, Centre Hospitalier Universitaire de Québec, Quebec City, Québec, Canada.
Jean-Pierre
JP
Bouchard
Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, Québec, Canada; Ontario Institute for Cancer Research, Toronto, Ontario, Canada.
Philip
P
Awadalla
Department of Medicine, University of Laval, Quebec City, Québec, Canada; Neuromuscular and Neurogenetic Disease Clinic, Centre Hospitalier Universitaire de Québec, Quebec City, Québec, Canada.
Nicolas
N
Dupré
Montreal Neurological Institute and Hospital, McGill University, Montreal, Québec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada.
Patrick A
PA
Dion
Montreal Neurological Institute and Hospital, McGill University, Montreal, Québec, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada. Electronic address: guy.rouleau@mcgill.ca.
Guy A
GA
Rouleau
D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D001483:Base Sequence; D002170:Canada; D004268:DNA-Binding Proteins / Q000235:genetics; D059472:Exome / Q000235:genetics; D056726:Genetic Association Studies; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics* / Q000502:physiology; D012313:RNA / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044465:White People
D004268:DNA-Binding Proteins; C518587:MATR3 protein, human; D034521:Nuclear Matrix-Associated Proteins; D016601:RNA-Binding Proteins; D012313:RNA
Amyotrophic lateral sclerosis; French-Canadian population; Genetic mutation; Matrin-3; Nuclear matrix protein and DNA/RNA binding protein