부산대학교 도서관

To investigate the genetic etiology of anophthalmia and microphthalmia, we used exome sequencing in a Caucasian female with unilateral microphthalmia and coloboma, bilateral optic nerve hypoplasia, ventricular and atrial septal defects, and growth delays. We found two sequence variants inSALL4- c.[575C>A], predicting p.(Ala192Glu), that was paternally inherited, and c.[2053G>C], predicting p.(Asp685His), that was maternally inherited. Haploinsufficiency forSALL4due 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. Our report is the first description of structural eye defects associated with two missense variants inSALL4inherited in trans; the absence of reported findings in both parents suggests that both sequence variants are hypomorphic mutations and that both are needed for the ocular phenotype.SALL4is expressed in the developing lens and regulatesBMP4, leading us to speculate that alteredBMP4expression was responsible for the eye defects, but we could not demonstrate alteredBMP4expressionin vitroafter using small interfering RNAs (siRNAs) to reduceSALL4expression. We conclude thatSALL4hypomorphic variants may influence eye development. [ABSTRACT FROM AUTHOR]