Fetal anomalies
Gene: C1QBPRemoved the Q2_23_promote_green tag as this gene has now been promoted to green.Created: 17 Oct 2023, 2:12 p.m. | Last Modified: 17 Oct 2023, 2:12 p.m.
Panel Version: 3.111
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 7 panels, inc. fetal anomalies, DDG2P, IEM, severe paediatric disorders. Associated with Combined oxidative phosphorylation deficiency 33 (AR). Notes in R21: DDG2P rating in original PAGE list: Probable for Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain Deficiencies. This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHsOutcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene to watch for further evidence. Alstrup et al., 2021 PMID 33977026: Siblings. Subject 1: first trimester combined screening = normal. Scan at 20weeks = small fetus with head circumference and abdominal circumference around -4SD, oligohydramnios and reduced fetal movements. Fetal MRI of cerebellum at 21weeks = no abnormalities. Subsequent scans: severe IUGR, extremity growth restriction, echogenic bowel, enlarged fetal heart with pericardial effusion, biventricular dysfunction and bradycardia. From 28-33weeks, progression of dilated cardiomyopathy and reduced biventricular function, pulmonary hypoplasia, anhydramnios and hydrops fetalis with ascites and generalised skin edema. 33wks -> stillbirth. Postnatal autopsy: also immature erythrocytes, focal dermal bullae, dysmorphic facial features, talipes equinovarus congenita, sandal gap, hydrothorax and hepatomegaly. Subject 2: 13+1wks = increased NT, abnormal flow in ductus venosus with negative a-wave and choroid plexus cysts. 15wks: HC and AC = -2SD and ventricular septum defect, confirmed at 17wks. Also abnormal contractility of the heart, pericardial effusion, bradycardia. 19+5wks: HC and AC = -3.3SD and myocardium was hyperechogenic. TOP at 20wks. PM: also large cyst bordering a dilated fourth ventricle, cerebellar hypoplasia, and multiple small periventricular cerebral hemorrhages in an otherwise normally developed cerebrum. Facial dysmorphisms, extremity contractures, sandal gap toes, underdeveloped ovaries, and a mediastinal cystic hygroma were also found. The placenta was small and hypoperfused. Feichtinger et al., 2017 PMID 28942965: Subject 1: oligohydramnios. Swollen face, hands and feet noticed at birth. 3do: cardiorespiratory arrest. Deteriorated. Died 18do (respiratory insufficiency). Twin brother unaffected. Subject 2: IUGR, oligohydramnios. Born by CS due to fetal heart rate failure. Cardiomegaly, hepatomegaly, lipid accumulation in liver. Died 4do (cardiorespiratory insufficiency). Conclusion: link to prenatal phenotypes (IUGR, oligohydramnios, anhydramnios, echogenic bowel, cardiac defects, hydrops fetalis, bradycardia). 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
Combined oxidative phosphorylation deficiency 33, OMIM:617713
Publications
This gene and phenotype were reviewed during a meeting on 21st October 2021 between representatives of the North Thames and Central & South R21 testing GLHs.
Clinical review and curation was performed by Lyn Chitty, Alison Male, Rowenna Roberts, Rhiannon Mellis (North Thames GLH) and Stephanie Allen, Denise Williams and Esther Kinning (Central & South GLH).
Outcome of review: May be fetally relevant but currently limited evidence, support adding to the Fetal anomalies panel as Amber gene to watch for further evidence.
Currently rated Green on the following other PanelApp panel(s): mitochondrial and inborn errors of metabolism
Details of review:
Becher et al 2020 (PMID: 32304219) reported a homozygous class 4 variant in a fetus with multiple anomalies and previous affected sibling but no further details published on the fetal phenotype.Created: 10 Aug 2022, 8:38 a.m. | Last Modified: 10 Aug 2022, 8:38 a.m.
Panel Version: 1.900
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Combined oxidative phosphorylation deficiency 33; Cardiomyopathy; Myopathy; Metabolic acidosis; Ologohydramnios
Publications
DDG2P rating in original PAGE list: Probable for Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain DeficienciesCreated: 11 Dec 2018, 9:04 a.m.
In the original PAGE file, MOP listed as All missense/in frame.Created: 8 Nov 2018, 4:45 p.m.
Mode of pathogenicity
Other - please provide details in the comments
Tag Q2_23_promote_green was removed from gene: C1QBP. Tag Q2_23_NHS_review was removed from gene: C1QBP.
Source Expert Review Green was added to C1QBP. Source NHS GMS was added to C1QBP. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Publications for gene: C1QBP were set to 32304219
Tag Q2_23_promote_green tag was added to gene: C1QBP. Tag Q2_23_NHS_review tag was added to gene: C1QBP.
Added phenotypes Combined oxidative phosphorylation deficiency 33, OMIM:617713 for gene: C1QBP
Phenotypes for gene: C1QBP were changed from Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain Deficiencies to Combined oxidative phosphorylation deficiency 33, OMIM:617713; Cardiomyopathy; Myopathy; Metabolic acidosis; Ologohydramnios
Publications for gene: C1QBP were set to
gene: C1QBP was added gene: C1QBP was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: C1QBP was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: C1QBP were set to Severe Neonatal-, Childhood-, or Later-Onset Cardiomyopathy Associated with Combined Respiratory-Chain Deficiencies