Pulmonary arterial hypertension
Gene: NFU1
After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remainsAmber. The GMS commented this is a mitochondrial disease gene, and part of widespread severe phenotype, dont think appopriate for this panel as although PAH may be presenting feature, it is not an isolated finding, more appropriate for mitochondrial disease panels, can stay amberCreated: 31 Jan 2023, 1:27 p.m. | Last Modified: 31 Jan 2023, 1:27 p.m.
Panel Version: 3.3
Comment on list classification: There is enough evidence to rate this gene as Green at the next GMS panel update - sufficient number of unrelated cases (>3) supported by a NFU1 deficiency rat model which exhibited PAH.Created: 26 May 2021, 2:49 p.m. | Last Modified: 26 May 2021, 2:49 p.m.
Panel Version: 2.15
Biallelic variants in this gene cause multiple mitochondrial dysfunctions syndrome, a severe neonatal onset disorder of systemic energy metabolism, resulting in weakness, respiratory failure, lack of neurologic development, leukodystrophy, lactic acidosis, and early death.
More than 50% of infant patients are found to display significant PAH, which can initially be an isolated and prominent finding (PMID: 22077971; 25918518; 28470589; 31516295; 32669393). Pulmonary samples from NFU1-deficient individuals with PAH showed obstructive vasculopathy with proximal and acinar arterial involvement (PMID: 22077971).
Humanised rare model of NFU1 deficiency showed features of mitochondrial dysfunction comparable to those observed in patients and also developed PAH (PMID: 31461310)
Sources: LiteratureCreated: 26 May 2021, 2:47 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Multiple mitochondrial dysfunctions syndrome 1, OMIM:605711; Pulmonary hypertension in early infancy
Publications
Tag Q2_21_rating was removed from gene: NFU1.
Gene: nfu1 has been classified as Amber List (Moderate Evidence).
gene: NFU1 was added gene: NFU1 was added to Pulmonary arterial hypertension. Sources: Literature Q2_21_rating tags were added to gene: NFU1. Mode of inheritance for gene: NFU1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NFU1 were set to 22077971; 25918518; 28470589; 31516295; 32669393; 31461310 Phenotypes for gene: NFU1 were set to Multiple mitochondrial dysfunctions syndrome 1, OMIM:605711; Pulmonary hypertension in early infancy Review for gene: NFU1 was set to GREEN