Amyotrophic lateral sclerosis/motor neuron disease
Gene: C9orf72Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanismCreated: 8 Nov 2021, 11:14 a.m. | Last Modified: 8 Nov 2021, 11:14 a.m.
Panel Version: 1.45
Comment on list classification: Made red due to reviewer's comments, and tier 1/tier 2 variants will not be relevent within this gene.Created: 13 Jun 2016, 10:41 a.m.
This gene is in the genetic guide to dementia and motor neurone disease section in the UCLH National Hospital for Neurology and Neurosurgery & Institute of Neurology (NHNN) Neurogenetics genetic testing manual, for testing of Amyotrophic lateral sclerosis: "The GGGGCC hexanucleotide repeat expansion in intron-1 of the C9orf72 gene is the most common cause of familial (50% of cases) and sporadic ALS (10% of cases). Interestingly a similar percentage of FTD cases were found to be caused by the same expansion."Created: 13 Jun 2016, 9:07 a.m.
non-coding hexanucleotide repeat expansion is associated with ALS and FTD in a dominant inheritance pattern with variable penetrance. I agree that an expanded repeat may not be detected by current NGS technology and would recommend, as is already suggested in eligability criteria, that this is tested prior to recruitment. Reporting of coding sequence variants in the gene would be unlikely to be clinically useful at present.
Associated with FTD and ALS.
Created: 9 Jun 2016, 7:23 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Frontotemporal Dementia, Amyotrophic Lateral Sclerosis
Mode of pathogenicity
Other
Variants in this GENE are reported as part of current diagnostic practice
The GGGGCC non-coding hexanucleotide expansion in C9orf72, which can cause familial ALS and FTD in an autosomal dominant fashion (high evidence), is not expected to be detected via current NGS technology. Although the repeat expansion may act partly through a loss-of-function mechanism at the epigenetic level, I am not aware of any coding sequence mutations in this gene that have yet been associated with ALS or FTD. Reporting of coding sequence variants in this gene would therefore be unlikely to be clinically useful at present. However, such variant data would of course be of considerable research interest.Created: 22 Apr 2016, 7:38 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
amyotrophic lateral sclerosis; frontotemporal dementia
Publications
Mode of inheritance for gene: C9orf72 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to Other
Publications for gene: C9orf72 were set to PMID: 21944778; 21944779; 25638642; 27059391; 23597494
Phenotypes for gene: C9orf72 were changed from Amyotrophic Lateral Sclerosis/Frontotemporal Dementia; Amyotrophic lateral sclerosis and/or frontotemporal dementia, 105550 -3; Hexanucleotide repeat expansion; Frontotemporal Dementia, Amyotrophic Lateral Sclerosis; amyotrophic lateral sclerosis; frontotemporal dementia; Frontotemporal Dementia, Amyotrophic Lateral Sclerosis to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Tag currently-ngs-unreportable tag was added to gene: C9orf72.
Promoted to version 1 on 19th December 2016 following external review and internal curation
This gene has been classified as Red List (Low Evidence).
This gene has been classified as Red List (Low Evidence).
Phenotypes for C9orf72 were set to Amyotrophic Lateral Sclerosis/Frontotemporal Dementia; Amyotrophic lateral sclerosis and/or frontotemporal dementia, 105550 -3; Hexanucleotide repeat expansion; Frontotemporal Dementia, Amyotrophic Lateral Sclerosis; amyotrophic lateral sclerosis; frontotemporal dementia; Frontotemporal Dementia, Amyotrophic Lateral Sclerosis
Mode of pathogenicity for C9orf72 was changed to Other - please provide details in the comments
Mode of inheritance for C9orf72 was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for C9orf72 were set to Amyotrophic Lateral Sclerosis/Frontotemporal Dementia; Amyotrophic lateral sclerosis and/or frontotemporal dementia, 105550 -3; Hexanucleotide repeat expansion; Frontotemporal Dementia, Amyotrophic Lateral Sclerosis; amyotrophic lateral sclerosis; frontotemporal dementia
Publications for C9orf72 were set to PMID: 21944778; 21944779; 25638642; 27059391; 23597494
Phenotypes for gene C9orf72 were set to Amyotrophic Lateral Sclerosis/Frontotemporal Dementia;Amyotrophic lateral sclerosis and/or frontotemporal dementia, 105550 -3; Hexanucleotide repeat expansion
Model of inheritance for gene C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
C9orf72 was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Eligibility statement prior genetic testing
Model of inheritance for gene C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
C9orf72 was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Expert
Model of inheritance for gene C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
C9orf72 was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Radboud University Medical Center, Nijmegen
Model of inheritance for gene C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
C9orf72 was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Illumina TruGenome Clinical Sequencing Services
Model of inheritance for gene C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
C9orf72 was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Expert
Model of inheritance for gene C9orf72 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
C9orf72 was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Source: Radboud University Medical Center, Nijmegen
C9orf72 was added to Amyotrophic lateral sclerosis/motor neuron diseasepanel. Sources: Illumina TruGenome Clinical Sequencing Services,Radboud University Medical Center, Nijmegen,Expert