Paediatric or syndromic cardiomyopathy
Gene: MIB1
Variants in PMID 23314057 have a relatively high population frequency in gnomad, out of keeping for a Mendelian disorder.
Evidence for gene-disease association seems to be mostly experimental rather than human. From ClinGen curation:
The MIB1 mRNA and protein are expressed in the heart (Jin et al, 2002, PMID: 12351649). In the mouse Luxán G et al used in situ hybridization to show that Mib1 is expressed in mouse endocardium and myocardium at embryonic day 9.5 (Luxan et al,2013, PMID: 23314057). Two cardiac specific Mib1 knock-out mouse models both had dilated heart with a thin compact myocardium and large, noncompacted trabeculae protruding toward the ventricular lumen. For the first model Nkx2.5-cre mice were used to knock out the Mib1flox/flox allele. In these mice cre is active in the endocardium and myocardium from E7.5 onward and they died at birth from valve dysfunction. For the second model cTnT-cre (also known as Tnnt2-cre) mice were used. In these mice cre is active from E8.0 onward in the myocardium. In addition, Mib1flox; cTnT-cre mice survive but showed a dilated heart with noncompaction and a significantly reduced ejection fraction (Luxan et al, 2013, PMID: 23314057, Captur et al, 2016, PMID: 27020702).Created: 26 Mar 2021, 9:41 a.m. | Last Modified: 26 Mar 2021, 9:41 a.m.
Panel Version: 1.19
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Left ventricular noncompaction 7, MIM# 615092; cardiomyopathy
Publications
The rating of this gene has been updated following NHS Genomic Medicine Service approval.Created: 3 Mar 2022, 1:12 p.m. | Last Modified: 3 Mar 2022, 1:12 p.m.
Panel Version: 1.65
This gene is associated with a relevant phenotype in OMIM and Gene2Phenotype. This gene has been tagged and will be submitted to the GMS specialist group for review.Created: 16 Apr 2021, 8:11 a.m. | Last Modified: 16 Apr 2021, 8:11 a.m.
Panel Version: 1.24
Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.Created: 2 Dec 2019, 3:58 p.m. | Last Modified: 2 Dec 2019, 3:58 p.m.
Panel Version: 0.16
Left ventricular noncompaction 7 OMIM#615092Created: 25 Mar 2019, 4:30 p.m.
HGMD variable phenotypes including intellectual disability.7 DM variants on HGMD - all but 1 are LVNC. Luxan Nature Med. 19: 193-201, 2013.PubMed: 23314057. Reported two families with a missense and nonsense variant tracking with LVNC. Functional studies undertaken showed reduction in NOTCH1 activity and zebra fish embryos were also created with the variants and found some deterimental effects. Note the earliest age of onset was 14 years reported so borderline paediatric to teen onset.Created: 25 Mar 2019, 4:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Tag Q2_21_rating was removed from gene: MIB1.
Source Expert Review Amber was added to MIB1. Rating Changed from Green List (high evidence) to Amber List (moderate evidence)
Tag Q2_21_NHS_review was removed from gene: MIB1.
Phenotypes for gene: MIB1 were changed from Left ventricular noncompaction 7 to Left ventricular noncompaction 7, OMIM:615092
Publications for gene: MIB1 were set to
Tag Q2_21_rating tag was added to gene: MIB1. Tag Q2_21_NHS_review tag was added to gene: MIB1.
Source NHS GMS was added to MIB1.
gene: MIB1 was added gene: MIB1 was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,London South GLH,South West GLH Mode of inheritance for gene: MIB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Phenotypes for gene: MIB1 were set to Left ventricular noncompaction 7