Fetal anomalies
Gene: PC
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 2nd March 2023 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, (North Thames GLH), and Stephanie Allen, Denise Williams, Anna de Burca 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 11 panels, inc. fetal anomalies, DDG2P, severe paediatric disorders, IEM. Associated with Pyruvate carboxylase deficiency (AR). Notes in R21: DDG2P rating in original PAGE list: Confirmed for PYRUVATE CARBOXYLASE DEFICIENCY. Outcome of review: Presentation of mitochondrial disorders can be variable, and most aren't obvious at birth. Therefore exclude unless the gene has been directly associated with a fetal presentation. Egloff et al., 2018 PMID 29752808: Case 2: cerebral anomalies identified in 3rd trimester. 1st and 2nd trimester USS didnt show any abnormalities. At 32 weeks: bilateral paraventricular cysts (19mm R and 11mm L), confirmed by MRI. Born at 41wks -> acute neurological distress -> died 6do due to hepatocellular deficiency. Neonatal transfontanellar USS showed bilateral hyperechogenicity of the periventricular white matter with subependymal cysts and periventricular cyst near frontal horn. MRI at 4do = massive periventricular cystic lesions in anterior region of frontal horns, lateral ventricles and temporal poles, also biparietal and bitemporopolar T2 hyperintense anomalies. No genetic studies done at this time but diagnosis confirmed after next affected and tested pregnancy (case 3). Case 3: 25wk USS = 3 paraventricular cysts (21wk ultrasound didnt show any anomalies). 33wk USS = bilateral subependymal cysts on frontal horns (2 R and 1 L) and cephalic biometry at 95th centile. Hom PC variant found. Born at 39wk. Died 40do. Mhanni et al., 2021 PMID 34485016: Diagnosis wasnt made prenatally, however abnormal phenotypes were seen following birth at 33wks prenatal onset. Born well but elevated citrulline on NBS -> PC c.1828G>A hom. MRI at 10do = periventricular white matter and subcortical white matter of bilateral cerebral hemispheres where more hyperintense on T2 weighted sequences when compared with unaffected twin. Affected twin also had multiple large periventricular cysts adjacent to frontal horns and body of lateral ventricles, smaller cyst in the L globus pallidus, dilatation of occipital horns and temporal horns of lateral ventricles. The presence of significant neuroimaging abnormalities in our patient at 33?weeks gestation supports previous reports that the neurodevelopmental sequelae seen in this form of congenital lactic acidosis are of prenatal onset. Pollock et al., 1986: Parents had had 4 normal children and 1 who died 6do with tachypnoea. Patients: twin pregnancy, both showed hydrocephalus antenatally and IUGR. Diagnosed with pyruvate carboxylase deficiency through biochemical testing. Brun et al., 1999 PMID 10323732: Patient 2: USS normal at 16.6wks. USS at 29.4wks: head circumference in upper range of control, hyperechogenicity of the lateral ventricular walls suggestive of intra-cerebral haemorrhage, synechiae in the lateral ventricles, and mild asymmetric ventricular dilatation. Progressive bilateral PVL and increasing biparietal diameter were noted later in pregnancy. Delivery at 33.5wks. Birth weight 50th centile, OFC >97th centile. Developed severe lactic acidaemia in 24 hours. Cerebral ultrasound at 2ho confirmed antenatal findings. Died 29ho. Coci et al., 2019 PMID 30870574: Patient 4: Fetal MRI revealed ventriculomegaly with septations and agenesis of the corpus callosum. Conclusion: link to prenatal phenotype (cerebellum/cerebral anomalies, IUGR). Relevant.Created: 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
Pyruvate carboxylase deficiency, OMIM:266150
Publications
This gene was reviewed by Anna de Burca (Genomics England Clinical Team), and at a Fetal Working Group call on July 19th 2019 by Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: Presentation of mitochondrial disorders can be variable, and most aren't obvious at birth. Therefore exclude unless the gene has been directly associated with a fetal presentation.Created: 25 Jul 2019, 8:04 a.m. | Last Modified: 25 Jul 2019, 8:04 a.m.
Panel Version: 0.311
DDG2P rating in original PAGE list: Confirmed for PYRUVATE CARBOXYLASE DEFICIENCYCreated: 11 Dec 2018, 9:05 a.m.
Tag Q2_23_promote_green was removed from gene: PC. Tag Q2_23_NHS_review was removed from gene: PC.
Source Expert Review Green was added to PC. Source NHS GMS was added to PC. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Phenotypes for gene: PC were changed from Pyruvate carboxylase deficiency, OMIM:266150; PYRUVATE CARBOXYLASE DEFICIENCY to Pyruvate carboxylase deficiency, OMIM:266150
Publications for gene: PC were set to
Tag Q2_23_promote_green tag was added to gene: PC. Tag Q2_23_NHS_review tag was added to gene: PC.
Source Expert Review Amber was added to PC. Added phenotypes Pyruvate carboxylase deficiency, OMIM:266150 for gene: PC Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Source Expert Review Red was added to PC. Rating Changed from Green List (high evidence) to Red List (low evidence)
gene: PC was added gene: PC was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: PC was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: PC were set to PYRUVATE CARBOXYLASE DEFICIENCY