Hydrocephalus
Gene: TTR
As discussed with the GMS Neurology Specialist Test Group webex call 11th July 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene RedCreated: 29 Jul 2019, 2:49 p.m. | Last Modified: 29 Jul 2019, 2:49 p.m.
Panel Version: 1.34
The 'treatable' tag has been added due to new therapies available that target this gene. Inotersen is an antisense oligonucleotide inhibitor of mutant and wild-type human transthyretin (TTR), developed and approved by NICE for the treatment of hereditary transthyretin amyloidosis (hATTR) (PMID: 30120737, https://www.nice.org.uk/guidance/hst9/chapter/1-Recommendations). Patisiran is a small interfering RNA (siRNA) molecule that targets the transthyretin gene (TTR) messenger mRNA (mRNA), to suppress both mutant and wild-type amyloid transthyretin (ATTR) protein production. This drug has been approved by NHSE for treatment of transthyretin-mediated amyloidosis (https://www.bbc.co.uk/news/health-48907976).Created: 9 Jul 2019, 12:30 p.m. | Last Modified: 9 Jul 2019, 12:30 p.m.
Panel Version: 1.30
Phenotypes
Amyloidosis, hereditary, transthyretin-related 105210
Publications
Comment when marking as ready: Not an appropriate phenotype for a hydrocephalus panel.Created: 29 Mar 2017, 1:27 p.m.
Comment on list classification: Hydrocephalus not a common feature. Adult onset progressive multi-system disorder. Not considered appropriate for hydrocephalus panel.Created: 29 Mar 2017, 1:26 p.m.
This is an autosomal dominant progressive multi-system disorder owing to abnormal protein deposition. It presents typically in the 3rd - 5th decade with polyneuropathy, autonomic neuropathy (GI / GU), cardiomyopathy and CNS symptoms. Hydrocephalus is listed as a linked feature, however it is not the predominant feature and many patients would not develop it. I do not see a hydrocephalus panel as the appropriate way of detecting this condition and caution would need to be applied in offering this gene to young participants, as this is most likely to represent a predictive test. Therefore, I would not include TTR on a primarily hydrocephalus panel.Created: 29 Mar 2017, 12:58 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Amyloidosis, hereditary, transthyretin-related 105210
Source NHS GMS was added to TTR.
Publications for gene: TTR were set to
Tag treatable tag was added to gene: TTR.
31.05.2017 - panel revised after internal curation and clinical review.
Phenotypes for TTR were set to Amyloidosis, hereditary, transthyretin-related 105210
This gene has been classified as Red List (Low Evidence).
Phenotypes for TTR were set to Amyloidosis, hereditary, transthyretin-related 105210; Familial Transthyretin Amyloidosis; Amyloidosis, Hereditary, Transthyretin-Related
This gene has been classified as Red List (Low Evidence).
TTR was added to Hydrocephaluspanel. Source: UKGTN
TTR was added to Hydrocephaluspanel. Source: Illumina TruGenome Clinical Sequencing Services
TTR was added to Hydrocephaluspanel. Sources: Radboud University Medical Center, Nijmegen
TTR was created by oniblock