Cardiomyopathy_Paediatric

Gene: MIB1

Red List (low evidence)

Evidence is mostly experimental:
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).

Variants in PMID 23314057 have a relatively high population frequency in gnomad, out of keeping for a Mendelian disorder.

Created: 26 Mar 2021, 9:39 a.m. | Last Modified: 26 Mar 2021, 9:39 a.m.

Panel Version: 0.60

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Left ventricular noncompaction 7, MIM# 615092; cardiomyopathy

Publications

• 23314057

I don't know

CHD: PMID: 30322850
4x probands - all missense except frameshift. All absent in gnomAD except for Ser520Arg (5 hets, 0 homs)
Only W271G and the fs demonstrated reduced NOTCh signaling
Mutant zebrafish were evaluated for degree of malformation

Association with LVNC disputed by clingen - 2 variants reported in PMID: 23314057 however the missense has 45 hets and the nonsense has 13 hets. Clingen also pointed out that there's too many carriers of LoF variants in gnomAD for gene association to be real

NO association with DCM by clingen

Created: 25 Mar 2021, 4:23 a.m. | Last Modified: 28 Mar 2021, 9:15 p.m.

Panel Version: 0.62

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Congenital heart disease

Publications

• 30322850
• 23314057