The ADAMTS18 gene is mutated in a patient with Early Onset Severe Retinal Dystrophy. (A) Fundus examination of patient A24 revealed attenuated retinal vessels, macular dystrophy, and diffuse mid-peripheral RPE mottling with myriads of tiny white and black dots. (B) Schematic representation, visualized with the Integrative Genomics Viewer (IGV) browser, of the mapped exome sequencing reads around the ADAMTS18 c.T3235 > C sequence variant in patient A24. The upper part shows the wild-type sequence and the coverage per base. The c.T3235 > C homozygous variant is shown in brown. Please note that the sequence variant shown in red corresponds to a described SNP (rs35478105). (C) Validation by Sanger sequencing of the c.T3235 > C in patient A24 while his parents and his unaffected brother are heterozygous for the variation (red arrows); the rs35478105 SNP is labeled by an asterisk. (D) The top diagram shows a schematic representation of the ADAMTS18 protein. The c.T3235 > C (p.C1079R) variant affects a cysteine residue localized within the third TSP type 1 motifs, which is highly conserved across evolution (red asterisk, bottom panel). (E) RNA in situ hybridization experiment showing that the murine Adamts18 is expressed in the adult mouse retina (see text for further details). ON, optic nerve.