Fetal anomalies
Gene: ENPP1The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 11:19 a.m. | Last Modified: 3 Mar 2022, 11:19 a.m.
Panel Version: 1.836
Comment on list classification: Following curation and clinical review it has been agreed that the associated phenotype is fetally-relevant and therefore this gene should be promoted to Green at the next GMS panel update (added 'Q4_21_rating' tag)Created: 2 Nov 2021, 4:56 p.m. | Last Modified: 2 Nov 2021, 4:56 p.m.
Panel Version: 1.764
This gene and phenotype were re-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: Confirmed that the phenotype is fetally relevant, support adding to the Fetal anomalies panel as a Green gene.
Details of review:
Phenotype is hypophosphataemic rickets / arterial calcification of infancy. Previously reviewed as not fetally relevant as not felt to be detectable in utero. New evidence considered from Aggarwal et al 2020 (PMID: 31742715), who report a fetus with homozygous missense variants presenting with hydrops and on post-mortem had macrocephaly and arterial calcification found on histopathology. Consanguineous couple with previous affected pregnancy.
Further reports of ENPP1 mutations with arterial calcification of infancy presenting as hydrops in PMID: 19521093 and PMID: 19813208. Additionally, ABCC6 is the other known GACI gene and is already Green on fetal anomalies panel so suggest ENPP1 should be the same for consistency.Created: 29 Oct 2021, 1:37 p.m. | Last Modified: 29 Oct 2021, 1:37 p.m.
Panel Version: 1.749
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Generalised arterial calcification of infancy (GACI)
Publications
This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Additional notes from clinical review: Not detectable in utero. Action taken: Demoted ENPP1 gene rating from Green to Red.Created: 24 Mar 2019, 4:30 p.m.
DDG2P rating in original PAGE list: Confirmed for HYPOPHOSPHATEMIC RICKETS, AUTOSOMAL RECESSIVE, 2 and Confirmed for ARTERIAL CALCIFICATION, GENERALIZED, OF INFANCY, 1.Created: 11 Dec 2018, 9:04 a.m.
Tag Q4_21_rating was removed from gene: ENPP1.
Source Expert Review Green was added to ENPP1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Gene: enpp1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: ENPP1 were changed from HYPOPHOSPHATEMIC RICKETS, AUTOSOMAL RECESSIVE, 2; ARTERIAL CALCIFICATION, GENERALIZED, OF INFANCY, 1 to Arterial calcification, generalized, of infancy, 1, OMIM:208000
Publications for gene: ENPP1 were set to
Tag Q4_21_rating tag was added to gene: ENPP1.
Source Expert Review Red was added to ENPP1. Rating Changed from Green List (high evidence) to Red List (low evidence)
Added phenotypes ARTERIAL CALCIFICATION, GENERALIZED, OF INFANCY, 1 for gene: ENPP1
gene: ENPP1 was added gene: ENPP1 was added to Fetal anomalies. Sources: Expert Review Green,PAGE DD-Gene2Phenotype Mode of inheritance for gene: ENPP1 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: ENPP1 were set to HYPOPHOSPHATEMIC RICKETS, AUTOSOMAL RECESSIVE, 2