Congenital Heart Defect

Gene: PKD1L1

Green List (high evidence)

Numerous families (6 families, 9 affected individuals) reported with heterotaxy and complex congenital heart defects, with biallelic variants (primarily nonsense, frameshift, splice site and a missense variant) in the PKD1L1 gene. Three reports with additional features (3079108, 30791085, 30791085), such as congenital asplenia, sideroblastic anemia, hydrops fetalis.

Several animal models suggest PKD1L1 plays a significant role in the development of L-R asymmetry and establish the L-R axis in vertebrate organisms, including mouse null and missense substitution models and a medaka knockout. Where complex congenital heart defects are often associated with laterality defects (ranging from situs inversus totalis (SIT) to situs

ClinVar: reports all published variants presented, plus 1 additional nonsense variant (not published). Summary: likely pathogenic/pathogenic (6 nonsense loss of function, 2 splice site and 1 missense variant), associated with autosomal visceral heterotaxy type 8, MIM 617205).
Sources: Literature

Created: 21 Nov 2023, 12:12 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Heterotaxy, visceral, 8, autosomal; HTX8 (MIM617205)

Publications

• PMID: 27616478
• 31026592
• 3079108
• 30791085
• 33655537