Dilated Cardiomyopathy and conduction defects

Gene: NKX2-5

Red List (low evidence)

NKX2-5 (NK2 homeobox 5)
EnsemblGeneIds (GRCh38): ENSG00000183072
EnsemblGeneIds (GRCh37): ENSG00000183072
OMIM: 600584, Gene2Phenotype
NKX2-5 is in 17 panels

2 reviews

Rebecca Whittington (South West GLH)

Green List (high evidence)

Atrial septal defect 7, with or without AV conduction defects OMIM#108900; Conotruncal heart malformations, variable OMIM#217095; Hypoplastic left heart syndrome 2 OMIM#614435; Hypothyroidism, congenital nongoitrous, 5 OMIM#225250; Tetralogy of Fallot OMIM#187500; Ventricular septal defect 3 OMMIM 614432
Created: 25 Mar 2019, 4:30 p.m.
HGMD: Four variants classed as DM and associated with DCM: Hanley 2016 (Hanley et al. BMC Medical Genetics (2016) 17:83): Two families with variants in the same codon I184. Some suggestion of variants tracking with disease, family members have mix of DCM and CHD such as VSD and ASD as well as conduction defects. Appears to have reduced disease penetrance so some evidence but not strong. 1 family tracks with disease in 2 generations but also found in four unaffected family members (reduced penetrance and possibly age of onset); second family variant tracks through 2 generations with four affected family members, but not seen in a family member with VSD and a second family member with VT. Neither variant on GnomAD. Yuan 2015 reports a variant fully penetrant tracking with DCM patients also had AF and AVB. Study of this variant in an insilico study suggests pathogenic: Abdul Samad PLoS One. 2016 May 6;11(5):e0153999. doi: 10.1371/journal.pone.0153999. eCollection 2016. Xu Int Heart J 2017; 58: 521-529: two patients with NKX2-5 vairants who presented with adult onset DCM but also previously had VSD and AVB, both variants were de novo following parental studies.
Created: 25 Mar 2019, 4:27 p.m.
BGL: Only tested in CHD patients.
Created: 25 Mar 2019, 4:24 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

I don't know

History Filter Activity

21 Feb 2019, Gel status: 1

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to NKX2-5. Mode of inheritance for gene NKX2-5 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

14 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

NKX2-5 was added to Dilated Cardiomyopathy and conduction defectspanel. Sources: Radboud University Medical Center, Nijmegen