Figure titles and legends
Figure 1A. Family pedigrees with juvenile-onset open-angle
glaucoma (JOAG) and EFEMP1 mutation status. Arrow indicates the
proband. Squares indicate male subjects; and circles refer to female
subjects. Slash through indicates a deceased individual. Solid symbols
indicate subjects diagnosed with JOAG; half-filled symbols indicate
subjects who carry the EFEMP1 variant but with no clinical signs
of glaucoma; and open symbols refer to subjects with no glaucoma and noEFEMP1 variant. Genotypes are heterozygous mutant (m/+) and wild
type (+/+). Figure 1B. Schematic diagram of EFEMP1 and
evolutionary conservation. EFEMP1 Genbank transcript
NM_001039348.3 and color-coded exons corresponding to the protein
domain. The mutations p.Asn80Tyr, p.Arg477Cys, and p.Ter494Glnext*29 are
located at highly conserved domains across several organisms.
Figure 2. Fundus images from a patient from Family B with EFEMP1
variant p.Ter494Glnext*29 (B-V:5). The image show damage to the optic
nerve but no evidence of subretinal deposits (drusen) characteristic of
Malattia Leventinese/Doyne Honeycomb dystrophy.
Figure 3. Single cell RNA sequencing EFEMP1 expression
and known early onset glaucoma genes from the human aqueous humor
outflow pathway. Comparative expression levels of EFEMP1 and
genes known to cause various types of early onset glaucoma. Plot
generated from the Broad Institute of MIT and Harvard’s Single Cell
Portal using data from “Cell atlas of aqueous humor outflow pathways in
eyes of humans and four model species provides insight into glaucoma
pathogenesis” by van Zyl et al, 2019.16
Figure 4 . Expression of EFEMP1 in COS-7 cells.Cultured
COS-7
cells transfected with wildtype and variant EFEMP1 and processed
with immunocytochemistry and the following stains: DAPI (nucleus),
CellLight ER-RFP (endoplasmic reticulum), Alexa 647 (EFEMP1protein), GFP (GFP expression reporter). Imaged using Leica SP8 confocal
microscope using 63x objective (glycerol immersion), digital zoom 2x.