Congenital Heart Defect

Gene: NKX2-6

Green List (high evidence)

Review updated - 3 unrelated families now reported

PMID 15649947 (Heathcote et al 2005) - first reported biallelic variants NKX2-6 associated with type 1 truncus arteriosis in a large consanguineous family previously described by (Abushaban et al 2003 - 12574981)

PMID 24421281 (Ta-Shma et al 2014) Subsequently reported, another consanguineous family with conotruncal defects (including VSD and TA) and homozygous nonsense NKX2-6 variants. One individual from that family was
also noted to have athymia

PMID 32198970 (Ritter et al 2019) - Reported compound het variants in x2 siblings with truncus arteriosus (2nd sibling diagnosed antenatally) from non-consanguineous family

Additional studies of NKX2-6 identified a
- heterozygous missense variant c.472A > C (p.Lys158Gln) that segregated with VSD (PMID 25380965 Wang et al 2015)
- heterozygous missense variant c.525G > C (p.Gln175His) that segregated in a family with atrial fibrillation (PMID 25319568 Wang et al 2014)

Included in PanelApp as biallelic inheritance but possibility of less severe phenotype with monoallelic inheritance possible - but one reported family only.

Created: 20 Dec 2021, 6:54 a.m. | Last Modified: 20 Dec 2021, 6:54 a.m.

Panel Version: 0.165

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Conotruncal heart malformations - MIM#217095; Persistent truncus arteriosus - MIM#217095

Publications

• 24421281
• 15649947
• 32198970
• 25380965
• 25319568