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| Fetal anomalies v1.900 | ASXL3 |
Rhiannon Mellis edited their review of gene: ASXL3: Added comment: 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 still limited evidence, support keeping as Amber gene for now. Details of review: Previously reviewed as Amber as 2 fetal cases in literature: one from PMID: 32565546 with short CC and metopic synostosis, one from PMID: 29316359 with distal arthrogryposis and cerebellar vermian hypoplasia. Now there is one more fetal case reported with arthrogryposis - PMID: 33820833; Changed publications to: PMID: 33820833; Changed phenotypes to: Arthrogryposis |
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| Fetal anomalies v1.880 | PLOD3 |
Rhiannon Mellis gene: PLOD3 was added gene: PLOD3 was added to Fetal anomalies. Sources: Literature,Expert Review Mode of inheritance for gene: PLOD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLOD3 were set to PMID: 18834968; PMID: 33743358 Phenotypes for gene: PLOD3 were set to Lysyl hydroxylase 3 deficiency; IUGR; Contractures Review for gene: PLOD3 was set to AMBER Added comment: This gene and phenotype were reviewed during a meeting on 21st July 2022 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rhiannon Mellis (North Thames GLH), and Stephanie Allen, Denise Williams, Esther Kinning and Anna de Burca (Central & South GLH). Outcome of review: May be fetally relevant, support adding to the Fetal anomalies panel as an Amber gene, pending more evidence. Rated Green on the following other PanelApp panel(s): Cataracts Details of review: Phenotype on OMIM includes potentially fetally detectable phenotypes: IUGR, contractures, cataracts (?whether congenital). Salo et al 2008 (PMID: 18834968) describes a proband with IUGR, flat facial profile, simple, low-set ears, shallow orbits, short, upturned nose, and downturned corners of the mouth. Skeletal features included talipes equinovarus, progressive scoliosis, osteopenia, and several pathologic fractures. A sib had IUGR and was stillborn, with finger contractures (but didn't seem to have molecular testing?). The fetal case in Cao et al 2021 had NT 5.2 mm (12/40), Reduced fetal movement (12/40), FGR (24/40), Enlarged posterior fossa (24/40), Intracranial haemorrhage (24/40), Clenched hands and fixated extended knees (24/40). Sources: Literature, Expert Review |
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| Fetal anomalies v1.880 | NEXN |
Rhiannon Mellis gene: NEXN was added gene: NEXN was added to Fetal anomalies. Sources: Literature,Expert Review Mode of inheritance for gene: NEXN was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: NEXN were set to PMID: 32058062; PMID: 33027564 Phenotypes for gene: NEXN were set to Cardiomyopathy Review for gene: NEXN was set to AMBER Added comment: This gene and phenotype were reviewed during a meeting on 21st July 2022 between representatives of the North Thames and Central & South R21 testing GLHs. Clinical review and curation was performed by Lyn Chitty, Alison Male, Rhiannon Mellis (North Thames GLH), and Stephanie Allen, Denise Williams, Esther Kinning and Anna de Burca (Central & South GLH). Outcome of review: Gene usually causes adult-onset AD cardiomyopathy. However, there may be a fetally relevant phenotype with biallelic variants. Support adding to the Fetal anomalies panel as an Amber gene, pending more evidence of fetal phenotype (only 2 reported unrelated cases to date). Currently rated Green on the following other PanelApp panel(s): Cardiomyopathy (dilated) Details of review: The fetal case in Sparks et al (PMID: 33027564) had pericardial effusion, ascites, cardiomegaly, dilation and hypertrophy of cardiac ventricles, hypoplastic and dysplastic aortic valve, diminished systolic function, fetal growth restriction, and was stillborn. 2 NEXN variants found in the fetus (1 mat inherited, 1 de novo) but unable to confirm phase. The fetal case in Rinaldi et al 2021 (PMID: 32058062) had Cardiomegaly, low contractility/outflow, fibroelastosis of right ventricle. The fetus was compound het for NEXN variants and parents were both unaffected het with normal echos. They'd had one previous pregnancy with same phenotype. Sources: Literature, Expert Review |
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| Fetal anomalies v1.836 | STIL | Arina Puzriakova Tag for-review was removed from gene: STIL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.836 | STIL | Arina Puzriakova commented on gene: STIL: The rating of this gene has been updated following NHS Genomic Medicine Service approval. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.835 | STIL |
Arina Puzriakova Source Expert Review Green was added to STIL. Rating Changed from Amber List (moderate evidence) to Green List (high evidence) |
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| Fetal anomalies v1.705 | PRKD1 | Arina Puzriakova Added comment: Comment on mode of inheritance: MOI was reassessed following a recent review by Zornitza Stark highlighting the potential involvement of biallelic variants. Currently the evidence for biallelic inheritance only suffices for an Amber rating and so I have kept the MOI as monoallelic but with a 'watchlist_MOI' tag to monitor for additional evidence. The Genomics England pipeline would still pick up biallelic cases under the current MOI. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.635 | KIDINS220 | Zornitza Stark reviewed gene: KIDINS220: Rating: GREEN; Mode of pathogenicity: None; Publications: 32909676; Phenotypes: limb contractures, ventriculomegaly, stillbirth; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.569 | STIL | Arina Puzriakova Phenotypes for gene: STIL were changed from MICROCEPHALY PRIMARY TYPE 7 to Microcephaly 7, primary, autosomal recessive, OMIM:612703; Microcephaly 7, primary, autosomal recessive, MONDO:0012989 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.568 | STIL | Arina Puzriakova Publications for gene: STIL were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.567 | STIL | Arina Puzriakova Classified gene: STIL as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.567 | STIL | Arina Puzriakova Added comment: Comment on list classification: Following curation and clinical review at GOSH it has been agreed that the associated phenotype is fetally-relevant. Therefore this gene should be promoted to Green at the next GMS panel update (added 'for-review' tag) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.567 | STIL | Arina Puzriakova Gene: stil has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.566 | STIL | Arina Puzriakova Tag for-review tag was added to gene: STIL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.187 | STIL | Rhiannon Mellis reviewed gene: STIL: Rating: GREEN; Mode of pathogenicity: None; Publications: 29230157; Phenotypes: Microcephaly 7, primary, autosomal recessive; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.185 | TXNDC15 |
Rhiannon Mellis gene: TXNDC15 was added gene: TXNDC15 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TXNDC15 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: TXNDC15 were set to Meckel Gruber syndrome Review for gene: TXNDC15 was set to GREEN Added comment: This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in October 2020. This gene has a Green evidence rating on at least one other related PanelApp panel (Cystic renal disease (super panel); Limb disorders; Rare multisystem ciliopathy Super panel). Clinical review and curation was performed by Lyn Chitty, Rhiannon Mellis, and Richard Scott. Outcome of review: Confirmed that phenotype is fetally-relevant: add to the Fetal anomalies panel as a Green gene. Comment from copied from skeletal ciliopathies panel: Shaheen et al. 2016 (PMID:27894351) report TXNDC15 variants in two consanguineous Saudi families that share the features of Meckel-Gruber syndrome (a ciliopathy phenotype). Phenotypes of both patients included polydactyly; one patients was still born, and one survived till 11 hours old. Furthermore, through an international collaboration, they were able to identify an additional Meckel-Gruber syndrome patient (Pakistani origin) with a homozygous truncating variant in this gene. The patient also had polydactyly, although a sibling presented similarly but with no polydactyl. Patient fibroblasts had aberrant ciliogenesis. Sources: Other Sources: Literature |
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| Fetal anomalies v1.99 | TRPM7 | Eleanor Williams reviewed gene: TRPM7: Rating: AMBER; Mode of pathogenicity: None; Publications: 32503408, 31423533; Phenotypes: Cardiac arrhythmia, stillbirth; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v1.95 | TRPM7 |
Zornitza Stark gene: TRPM7 was added gene: TRPM7 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: TRPM7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TRPM7 were set to 32503408; 31423533 Phenotypes for gene: TRPM7 were set to Cardiac arrhythmia, stillbirth Review for gene: TRPM7 was set to AMBER Added comment: I am not sure if genes linked to stillbirth belong on this panel. This gene encodes an ion channel expressed in the nervous and cardiac systems. It has previously been associated with ALS/dementia in the Guam population, but the variant in question, p.Thr1482Ile is present in >23,000 hets in gnomad, which is out of keeping for a rare Mendelian disorder. Note recent publication associating missense variants with cardiac arrhythmia and stillbirth, with some functional data provided to substantiate effect of variant on protein function but not necessarily establish gene-disease association. Sources: Literature |
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| Fetal anomalies v1.64 | GREB1L |
Rebecca Foulger gene: GREB1L was added gene: GREB1L was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: GREB1L was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: GREB1L were set to 29261186 Phenotypes for gene: GREB1L were set to Renal hypodysplasia/aplasia 3, 617805; renal agenesis Added comment: Added to Fetal panel based on PMID:29261186 (Boissel et al., 2018) who performed WES in 101 fetuses or stillborns who presented prenatally with severe anomalies. In 2 cases presenting with renal agenesis, de novo variants in GREB1L were identified (p.A968V and p.S98X). Sources: Literature |
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| Fetal anomalies v1.59 | GJB2 | Rebecca Foulger commented on gene: GJB2: Note that GJB2 is no longer present on the DD panel of Gene2Phenotype. All GJB2 phenotypes (May 2020) are associated with the Gene2Phenotype skin panel. Red rating is still appropriate for this Fetal panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.367 | BICD2 | Rebecca Foulger commented on gene: BICD2: PMID:29274205 (Ahmed et al., 2018) report a stillborn female fetus (case 4) with pterygia and arthrogryposis with a heterozygous likely-pathogenic variant in BICD2. Phenotypes included an abnormal fetal position with fixed limbs, hydrops fetalis and polyhydramnios. A heterozygous p.Asn700Lys variant in BICD2 was revealed. However, compound het variants of unknown significance in AGRN were also identified, so the authors can not be certain that BICD2 is the causative variant. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.218 | MYT1 | Rebecca Foulger commented on gene: MYT1: Berenguer et al 2017 (PMID:28612832) identified a third (de novo) MYT1 variant in a patient with OAVS: c.323C>T p.Ser108Leu from a cohort of 57 new patients with a typically heterogeneous OAVS. From functional studies, it's still unclear how these variants impact retinoic acid signaling and contribute to the phenotype. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.9 | STIL | Rebecca Foulger reviewed gene: STIL: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Fetal anomalies v0.1 | STIL |
Rebecca Foulger gene: STIL was added gene: STIL was added to Fetal anomalies. Sources: PAGE DD-Gene2Phenotype,Expert Review Amber Mode of inheritance for gene: STIL was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: STIL were set to MICROCEPHALY PRIMARY TYPE 7 |
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