Fig. 1.

Fig. 1. Biallelic variants in CEP76 cause syndromic ciliopathies.

(A) Pedigrees are shown for available individuals (W, WT; M, mutant allele; M1, p.Ile28Metfs*7; M2, p.Leu508Profs*13; M3, c.1122G>A; M4, p.Val24Asp; M5, p.Ile101Thr; M6, p.Val265Met; M7, p.Phe511Ile; M8, p.Trp291del; M9, p.Leu166Pro; M10, p.Cys478Arg; M11, p.Pro103Ser; M12, p.His301Glnfs*6; M13, p.Arg568Pro). Blue arrows, individuals subjected to ES/GS. Family generation number, roman numerals (left). Circles, females; squares, males; unfilled shapes, unaffected; black filled shapes, affected; gray filled shapes, affected with unknown or unrelated disorder; diagonal line, deceased. Double lines indicate consanguinity. (B) Multimodal imaging of the family 5 proband (age, 35 years). (a) The fundus image (right eye) shows pigmentary changes and vessel narrowing consistent with a rod cone dystrophy. (b) Infrared reflectance (left eye) shows macular anomalies. (c and d) Fundus autofluorescence (both eyes) shows peripheral hypoautofluorescent spots with concentric foveal zones, a medial grayish zone, and a central large hypoautofluorescent foveola. (e and f) Optical coherence tomography of the right retina (e) and left retina (f) and loss of outer nuclear layer except subfoveal, with disorganized hyperreflective bands (white arrow heads). (C) Multimodal imaging of the family 7 proband (age, 26 years): (a) Fundus autofluorescence shows a hyperfluorescent ring (yellow arrow). (b) Fundus shows peripheral pigmentary changes and arteriolar narrowing. (c). Goldmann visual fields show mild constriction and central scotoma. (d and e) Optical coherence tomography (right retina) of photoreceptor thinning outside the fovea (outside of vertical yellow marks) and central preservation (between yellow marks). Retinal layers are shown, as described elsewhere (75). ONL, outer nuclear layer; INL, inner nuclear layer. (D) Brain magnetic resonance imaging (age, 3.5 months). (a) Midline-sagittal T1 shows a small and dysplastic vermis (arrowhead). (b) Para-midline-sagittal T1 shows a thickened and horizontalized superior cerebellar peduncle (arrow). (c) Axial-sagittal T1 shows a molar tooth sign.