Adult onset neurodegenerative disorder
Gene: HNRNPA1
only one family reported in association with IBMPFD3: progressive predominantly proximal muscle weakness plus Paget disease of the bone, age of onset between 35-43, no congnitive impairment or motor neuron dysfunction (D314V) - red for this disorder. ALS - neurodegenerative disorder characterised by death of motor neurons in brain, brainstem and spinal cord - 2 cases identified: one at same residue as above (D314N) and another nearby n319S. Third case reported by Naruse (P340A). Functional evidence supports pathogenicity for 2 of the variants. fourth case with different amino acid change P340S supported by segregation data - greenCreated: 2 Sep 2019, 4:06 p.m. | Last Modified: 2 Sep 2019, 4:06 p.m.
Panel Version: 1.99
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
?Inclusion body myopathy wtih early-onset Paget disease without frontotemporal dementia type 3 615424, ALS type 20 615426
Publications
Mode of pathogenicity
Other - please provide details in the comments
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
?Inclusion body myopathy wtih early-onset Paget disease without frontotemporal
Publications
Variants in this GENE are reported as part of current diagnostic practice
Review and rating from Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group. All the green and amber, except for the genes with triplet repeats, were reviewed.Created: 2 Sep 2019, 4:46 p.m. | Last Modified: 2 Sep 2019, 4:46 p.m.
Panel Version: 1.101
Review and rating submitted by Nick Beauchamp (Sheffield Diagnostic genetics Service), on behalf of Yorkshire and North East GLH for GMS Neurology specialist test group.Created: 23 Jul 2019, 3:51 p.m. | Last Modified: 23 Jul 2019, 3:51 p.m.
Panel Version: 1.74
Review and rating submitted byJames Polke (North Bristol NHS Trust), unless specified in the review comment, on behalf of London North GLH for GMS Neurology specialist test group.Created: 23 Apr 2019, 5:35 p.m.
Phenotypes for gene: HNRNPA1 were changed from ?Inclusion body myopathy wtih early-onset Paget disease without frontotemporal to ?Inclusion body myopathy wtih early-onset Paget disease without frontotemporal dementia type 3, OMIM:615424, Amyotrophic lateral sclerosis 20, OMIM:615426
Publications for gene: HNRNPA1 were set to 23455423
Source Wessex and West Midlands GLH was added to HNRNPA1.
Publications for gene HNRNPA1 were changed from to 23455423
Source Yorkshire and North East GLH was added to HNRNPA1.
Source NHS GMS was added to HNRNPA1.
Source London North GLH was added to HNRNPA1.
Louise Daugherty: Comment on phenotypes: amended
Added phenotypes ?Inclusion body myopathy wtih early-onset Paget disease without frontotemporal for gene: HNRNPA1
gene: HNRNPA1 was added gene: HNRNPA1 was added to Neurodegenerative disorders - adult onset. Sources: Expert Review Green Mode of inheritance for gene: HNRNPA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: HNRNPA1 were set to ?Inclusion body myopathy wtih early-onset Paget disease without frontotemporal