Am J Med Genet A. 2025 Oct 29:e64288. doi: 10.1002/ajmg.a.64288. Online ahead of print.
ABSTRACT
We report a 15-year-old female with hypoplastic left heart syndrome and a strong family history of congenital heart defects. Quad genome sequencing was performed following negative chromosomal microarray and congenital structural heart disease gene panel testing, revealing a heterozygous 144 kb deletion encompassing exons 4-14 of RBFOX2, the entirety of the APOL5 gene, and exon 3 of APOL6 in all affected family members. Although RBFOX2 has been implicated in causing hypoplastic left heart syndrome in animal models, and variants in this gene are enriched in patients with congenital heart disease, this report establishes loss-of-function variants in RBFOX2 as an autosomal dominant cause of hypoplastic left heart syndrome. Furthermore, this case highlights the power of genome sequencing in identifying causative variants in patients who have received nondiagnostic array and panel testing.
PMID:41159281 | DOI:10.1002/ajmg.a.64288
