SALL4 deletion and renal and cardiac defects associated with VACTERL association

Abstract

Abstract Congenital Anomalies of the Kidney and Urinary Tract [CAKUT] can be a part of the VACTERL association, which represents the non-random combination of the following congenital anomalies: Vertebral anomalies, anal anomalies, cardiac anomalies, tracheal-esophageal anomalies, renal anomalies, and limb anomalies. VACTERL association is generally considered to be a non-genetic condition. Exceptions include a patient with a heterozygous nonsense SALL4 variant and anal stenosis, tetralogy of Fallot, sacro-vertebral fusion, and radial and thumb anomalies. SALL4 encodes a transcription factor that plays a critical role in renal morphogenesis. Here we report a patient with VACTERL association and a heterozygous 128-kb deletion spanning SALL4 who presented with renal hypoplasia, radial and atrio-septal defects, and patent ductus arteriosus. The present report of SALL4 deletion, in addition to a previously reported patient with VACTERL association phenotype and SALL4 nonsense mutation, further supports the notion that SALL4 haploinsufficiency can lead to VACTERL association.