Fetal anomalies
Gene: MN1The 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: New gene added by Rhiannon Mellis (GOSH). Multiple unrelated individuals (>20) described with a complex developmental disorder and de novo truncating MN1 variants. This gene will be flagged for review to determine whether the phenotype is fetally-relevant and there is enough evidence to include as Green.
Plausible that some features of the disorder, such as craniofacial abnormalities and structural brain anomalies may be detected prenatally. However based on published clinical descriptions, antenatal history was uneventful in most cases - but reports did include fetal brain anomalies (1), NICU admission (1) and IUGR (2). Similarly, neonatal problems were only reported in a few patients but included respiratory issues (3), abnormal ABR (1), congenital diaphragmatic hernia (1), perinatal hypoxia (1), congenital hypothyroidism (1), hearing impairment (1) and SCBU admission (1) (see Supplementary material in PMID: 31834374)Created: 18 Jan 2021, 1:22 p.m. | Last Modified: 18 Jan 2021, 1:22 p.m.
Panel Version: 1.155
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: Agreed that the phenotype is fetally relevant (structural brain abnormalities e.g. polymicrogyria, cerebellar hypoplasia, craniofacial features etc.) support adding to the Fetal anomalies panel as a Green gene.Created: 29 Oct 2021, 3:28 p.m. | Last Modified: 29 Oct 2021, 3:28 p.m.
Panel Version: 1.749
Copied from MN1 review on Cortical malformations panel:
Associated with phenotype in OMIM, and a probable gene for MN1 C-terminal truncation syndrome in G2P.
Over 20 unrelated probands reported with heterozygous MN1 truncating variants, associated with a distinct phenotype which includes DD, craniofacial abnormalities, hearing loss, and structural abnormalities in the brain (e.g. polymicrogyria, dysmorphic corpus callosum and anomalies of the cerebellum - rhombencephalosynapsis).
Most variants cluster in the C-terminal, and all were predicted to escape NMD. Authors postulated that the resulting truncated protein may have a dominant-negative or gain-of-function effect. Also phenotypically supportive knockout mouse model.
Sources: LiteratureCreated: 30 Nov 2020, 4:17 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
CEBALID syndrome, 618774
Publications
Mode of pathogenicity
Other
Tag for-review was removed from gene: MN1. Tag Q4_21_rating was removed from gene: MN1.
Source Expert Review Green was added to MN1. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q4_21_rating tag was added to gene: MN1.
Tag for-review tag was added to gene: MN1.
Gene: mn1 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: MN1 were changed from CEBALID syndrome, 618774 to CEBALID syndrome, OMIM:618774; CEBALID syndrome, MONDO:0032908
gene: MN1 was added gene: MN1 was added to Fetal anomalies. Sources: Literature Mode of inheritance for gene: MN1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Publications for gene: MN1 were set to 31834374; 31839203; 15870292 Phenotypes for gene: MN1 were set to CEBALID syndrome, 618774 Mode of pathogenicity for gene: MN1 was set to Other Review for gene: MN1 was set to GREEN