Amyotrophic lateral sclerosis/motor neuron disease
Gene: OPTNComment on publications: PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."
PMID: 26503823
PMID: 26303227 "We conclude that: (i) OPTN mutations are associated with ALS
(ii) optineurin protein is present in a subset of the extramotor inclusions of C9ORF72-ALS
(iii) It is not uncommon for multiple ALS-causing mutations to occur in the same patient
and (iv) studies of optineurin are likely to provide useful dataregarding the pathophysiology of ALS and neurodegeneration."
PMID: 26203661
PMID: 25943890
PMID: 25859013 - functional evidence
PMID: 25681989Created: 24 Jan 2024, 10:13 a.m. | Last Modified: 24 Jan 2024, 10:13 a.m.
Panel Version: 1.69
This gene is on the ALS/MND NGS Panel in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual: "OPTN mutations which maybe recessive in inheritance or dominant with reduced penetrance". Multiple cases and variants reported in OMIM and within literature search, with functional evidenc studies also supporting a role of the variants in the disease.Created: 15 Jun 2016, 1:23 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
familial amyotrophic lateral sclerosis (ALS12)
Publications for gene: OPTN were set to PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."; PMID: 26503823; PMID: 26303227 "We conclude that: (i) OPTN mutations are associated with ALS; (ii) optineurin protein is present in a subset of the extramotor inclusions of C9ORF72-ALS; (iii) It is not uncommon for multiple ALS-causing mutations to occur in the same patient; and (iv) studies of optineurin are likely to provide useful dataregarding the pathophysiology of ALS and neurodegeneration."; PMID: 26203661; PMID: 25943890; PMID: 25859013 - functional evidence; PMID: 25681989
Phenotypes for gene: OPTN were changed from Amyotrophic Lateral Sclerosis, Recessive; Glaucoma 1, open angle, E, 137760 to Amyotrophic lateral sclerosis 12 with or without frontotemporal dementia, OMIM:613435
Promoted to version 1 on 19th December 2016 following external review and internal curation
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Publications for OPTN were set to PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."; PMID: 26503823; PMID: 26303227 "We conclude that: (i) OPTN mutations are associated with ALS; (ii) optineurin protein is present in a subset of the extramotor inclusions of C9ORF72-ALS; (iii) It is not uncommon for multiple ALS-causing mutations to occur in the same patient; and (iv) studies of optineurin are likely to provide useful dataregarding the pathophysiology of ALS and neurodegeneration."; PMID: 26203661; PMID: 25943890; PMID: 25859013 - functional evidence; PMID: 25681989
Publications for OPTN were set to PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."; PMID: 26503823; PMID: 26303227 "We conclude that: (i) OPTN mutations are associated with ALS; (ii) optineurin protein is present in a subset of the extramotor inclusions of C9ORF72-ALS; (iii) It is not uncommon for multiple ALS-causing mutations to occur in the same patient; and (iv) studies of optineurin are likely to provide useful dataregarding the pathophysiology of ALS and neurodegeneration."; PMID: 26203661; PMID: 25943890
Publications for OPTN were set to PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."; PMID: 26503823; PMID: 26303227 "We conclude that: (i) OPTN mutations are associated with ALS; (ii) optineurin protein is present in a subset of the extramotor inclusions of C9ORF72-ALS; (iii) It is not uncommon for multiple ALS-causing mutations to occur in the same patient; and (iv) studies of optineurin are likely to provide useful dataregarding the pathophysiology of ALS and neurodegeneration."; PMID: 26203661
Publications for OPTN were set to PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."; PMID: 26503823
Publications for OPTN were set to PMID: 26566915 - "Here, we report a Chinese family spanning three generations with ALS8 caused by the same VAPB-P56S mutation detected in these cohorts, but which in its initial manifestation displays different features. We also detected a R545Q variant of optineurin (OPTN) in this family and which was previously considered a pathogenic mutation. However, our analysis showed that OPTN-R545Q is benign and that VAPB-P56S accounts for the phenotype."
Mode of inheritance for OPTN was changed to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Model of inheritance for gene OPTN was set to BIALLELIC, autosomal or pseudoautosomal
OPTN was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Expert
Model of inheritance for gene OPTN was set to BIALLELIC, autosomal or pseudoautosomal
OPTN was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Radboud University Medical Center, Nijmegen
Model of inheritance for gene OPTN was set to BIALLELIC, autosomal or pseudoautosomal
OPTN was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Illumina TruGenome Clinical Sequencing Services
Model of inheritance for gene OPTN was set to BIALLELIC, autosomal or pseudoautosomal
OPTN was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Expert
Model of inheritance for gene OPTN was set to BIALLELIC, autosomal or pseudoautosomal
OPTN was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Radboud University Medical Center, Nijmegen
OPTN was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Expert