Fetal anomalies
Gene: DARS2
The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.Created: 10 Oct 2023, 3:39 p.m. | Last Modified: 10 Oct 2023, 3:39 p.m.
Panel Version: 3.111
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
This gene and phenotype were reviewed during a meeting on 23rd Feb 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Natalie Chandler (North Thames GLH), and Stephanie Allen, Esther Kinning and Megan Horton-Bell (Central & South GLH). Outcome of review: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.Created: 5 May 2023, 3 p.m. | Last Modified: 5 May 2023, 3 p.m.
Panel Version: 3.8
On 18 panels, inc. fetal anomalies, IEM, DDG2P, IEM, severe paediatric disorders. Associated with Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (AR). Notes in R21: Rating in original PAGE file: 'both DD and IF' for LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION. Changed rating to Amber to reflect DDG2P Disease confidence of 'DD and IF' for LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION. Outcome of review: Phenotype is not fetally-relevant. Additional notes from clinical review: Slowly progressive and manifests later. Action taken: Demoted DARS2 gene rating from Amber to Red. Stellingwerff et al., 2021 PMID 33977142: LBSL285/281/292/294/293/295 all had microcephaly reported in Pregnancy/delivery. LBSL286 reduced fetal movements. MRI characteristics: LBSL293: antenatal MRI = increased number of tortuous vessels, cerebrum atrophy and hypoplasia, cerebral cortex signal abnormality. Conclusion: weak link to prenatal phenotype (microcephaly, 1 patient with abnormal antenatal brain MRI). ?RelevantCreated: 5 May 2023, 3 p.m. | Last Modified: 5 May 2023, 3 p.m.
Panel Version: 3.8
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105
Publications
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Originally rated Amber based on DDG2P Disease confidence of 'both DD and IF' for at least one disorder. Outcome of review: Phenotype is not fetally-relevant. Additional notes from clinical review: Slowly progressive and manifests later. Action taken: Demoted DARS2 gene rating from Amber to Red.Created: 29 Apr 2019, 12:28 p.m.
Changed rating to Amber to reflect DDG2P Disease confidence of 'DD and IF' for LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION.Created: 12 Feb 2019, 2:32 p.m.
Rating in original PAGE file: 'both DD and IF' for LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATIONCreated: 6 Dec 2018, 10:07 a.m.
Tag Q2_23_promote_green was removed from gene: DARS2. Tag Q2_23_NHS_review was removed from gene: DARS2.
Source Expert Review Green was added to DARS2. Source NHS GMS was added to DARS2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: DARS2 were changed from LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION; Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105 to Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105
Publications for gene: DARS2 were set to
Tag Q2_23_promote_green tag was added to gene: DARS2. Tag Q2_23_NHS_review tag was added to gene: DARS2.
Source Expert Review Amber was added to DARS2. Added phenotypes Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, OMIM:611105 for gene: DARS2 Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Source Expert Review Red was added to DARS2. Rating Changed from Amber List (moderate evidence) to Red List (low evidence)
Source Expert Review Amber was added to DARS2. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
gene: DARS2 was added gene: DARS2 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: DARS2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: DARS2 were set to LEUKOENCEPHALOPATHY WITH BRAINSTEM AND SPINAL CORD INVOLVEMENT AND LACTATE ELEVATION