This study identified a novel gene – MGRN1 (mahogunin ring finger 1) – implicated in congenital fetal malformations. A family experienced two pregnancies with fetuses presenting unexplained severe heart and laterality defects. ‘Genomic autopsy’ of affected cases uncovered a rare homozygous defect in MGRN1, regulating early development and left-right patterning. The observed human malformations closely resembled developmental defects observed in Mgrn1-deficient mouse models, strengthening the biological link. Our findings highlight the power of detailed genetic investigation after fetal death, including previously unknown disease genes. Such discoveries improve diagnosis, clarify recurrence risks, and support families in making informed decisions about future pregnancies. (https://jmg.bmj.com/content/early/2026/03/04/jmg-2025-111380 )