Congenital Heart Defect

Gene: CRELD1

Red List (low evidence)

Agree. LIMITED by ClinGen.

Created: 22 Nov 2023, 4:21 a.m. | Last Modified: 22 Nov 2023, 4:21 a.m.

Panel Version: 0.352

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Atrioventricular septal defect, susceptibility to, 2; Atrioventricular septal defect, partial, with heterotaxy syndrome MIM#606217

Red List (low evidence)

A patient with a missense CRELD1 variant was reported to have cardiac defects including coarctation of aorta, double inlet left ventricle and transposition of the great arteries (PMID: 22740159).
46 probands harbouring 21 other unique CRELD1 variants have been reported in patients with phenotypes including atrioventricular canal defects, atrial septal defects, dextrocardia, heterotaxy and Tetralogy of Fallot; however, these variants had either a high gnomAD minor allele frequency or low REVEL score (PMIDs: 12632326, 15857420, 18076106, 24927998, 22740159, 29054759, 34328347, 21413875, 21080147, 28798025, 36011280).
Incomplete penetrance observed (PMID: 12632326).
May increase risk of atrioventricular septal defect (AVSD) when combined with other risk factors such as trisomy 21 (PMID: 23040494).
Three functional studies have shown that Creld1 knockout mice have defects in cardiac development (PMIDs: 25328912, 24697899, 33773999).
Insufficient evidence that variants in this gene are causative of congenital heart disease.

Created: 19 Nov 2023, 1:18 p.m. | Last Modified: 19 Nov 2023, 1:18 p.m.

Panel Version: 0.315

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

Phenotypes
Atrioventricular septal defect, susceptibility to, 2; Atrioventricular septal defect, partial, with heterotaxy syndrome MIM#606217

Publications

• (PMID: 22740159
• 12632326
• 23040494
• 25328912
• 24697899
• 33773999)