Figure 1.

Genetic, brain, and retinal alterations associated with heterozygous CASK mutation. (A) Sanger sequences showing the de novo heterozygous splice variant in exon 24 (NM_001126054:exon24:c.2233+1G>A). (B) The schematic of exon skipping. (C) CASK. Reverse-transcription PCR with primers (arrows in panel B) in exons 25 and 23 on cDNA of the patient and subsequent sequencing confirmed exon 24 skipping (a lower band indicated by the arrow compared with control). (D, E) Magnetic resonance images of brain indicate no specific midline structural defect or white matter lesion. (F) A fundoscopic image from this haploinsufficient 3-year-old girl who was diagnosed with ONH. Note the pale, hypoplastic optic disc (as compared with a fundoscopy image from a 3.5-year-old girl without ONH; Supplementary Fig. S1).