Haploinsufficiency for SALL4 due to nonsense or frameshift mutations has been associated with acro-renal ocular syndrome that is characterized by eye defects including Duane anomaly and coloboma, in addition to radial ray malformations and renal abnormalities.
In addition, numerous mutations affecting the Sall4 gene have been discovered and clinically linked to a series of congenital abnormalities, such as Duane/Duane-related syndromes, ventricular septal defect and premature ovarian failure.
SALL4 represents the first identified Duane syndrome gene and the second malformation syndrome resulting from mutations in SAL genes and likely plays a critical role in abducens motoneuron development.