Fig. 1

Fig. 1 MAB21L2 variants in individuals with bilateral microphthalmia, including the genomic context of the deletion identified in Family 2.

A Pedigree and phenotypic images of the eyes of affected members of Family 1. The proband (II.1, black arrow) shows bilateral microphthalmia and iris coloboma (and has choroid and retinal coloboma, right cataract and left aphakia). His half-brother (II.2) shows bilateral iris coloboma (and has choroid and retinal colobomas, with nystagmus). Their mother (I.2) has a normal external eye appearance (with a small unilateral optic disc coloboma). All three individuals are heterozygous for the missense variant MAB21L2 p.(Trp113Ser). B Pedigree of Family 2. The proband (III.5, black arrow) presented with bilateral microphthalmia (wearing early socket expanders in the photo), orbital cysts and microcephaly. A short upturned nose and prominent philtral pillars can be seen. Her mother (II.2) had very subtle bilateral central anterior lens suture opacities; her father was unavailable. III.5 is homozygous for an ~ 113.5 kb deletion ~ 19 kb upstream of MAB21L2, inherited from her heterozygous mother. C Schematic image of the deleted region identified in Family 2 showing relative positions of LRBA and MAB21L2 (blue, with LRBA exon numbers indicated underneath), evolutionary non-coding conserved elements (CEs) within the deleted region, CNV location (red) and Sanger sequencing of proband demonstrating the breakpoints (sequencing of the breakpoint was performed for the negative strand only, for clarity the chromatogram shown is the reverse complement). CEs 7 and 8 contain the regulatory sequences Ma and Mb, respectively, identified by Tsang et al. ²⁸.