Fig. 1. Phenotype documentation and family pedigrees.

(I) Proband 1: (a) Retinal imaging of the right and left eye showing some retinal pigmentary changes and narrowing of the vessels. The optic nerve is overexposed and only had mild pallor. (b) Optical coherence tomography (OCT) centered on the macula showing thinning of the outer retina. (c) MAIA™ microperimetry showing decreased retinal sensitivity (black dots) despite decent vision. This leads to fixation instability (turquoise blur from fixation points). (d) Chest X-ray, lateral and anterior–posterior (AP) view showing normal size and chest structure. The pedigree shows segregation of the variants with the phenotype. Filled symbol: affected, arrow: proband. (II) Proband 2: (a) Wide field imaging of the retina of proband 2 showing equatorial bone spiculing changes characteristic of retinitis pigmentosa (RP). (b) Wide field fundus autofluorescence showing a hyperfluorescent area that represents the limits of the functional retina. (c) OCT imaging showing thinning of the outer retina. (d) Left: normal chest X-ray (AP) and right: normal hand X-ray. This pedigree shows consanguinity with very little information about family members who were not available for segregation analysis. Diamond shape symbol with no number: uncertain number of relatives, unknown gender. (III) Proband 3: (a) Fundus autofluorescence showing retinal pigment epithelium atrophy (dark spots throughout). The right eye has a hyperfluorescent ring outlining viable retina. (b) Below is a retina photograph showing attenuated vessels, a marker of photoreceptor degeneration. (c) The OCT shows retinal thinning. Pedigree of the family is also showing an autosomal recessive inheritance pattern and consanguinity. This proband was genotyped through a large genome sequencing initiative, and family members were not available for segregation analysis. Diamond shape symbol with number: number of children, unknown gender. (IV) Proband 4: (a) Wide field fundus autofluorescence showing pigmentary changes and a hyperfluorescent ring larger than for proband 2 though they are the same age. This suggests a larger field of vision. (b) OCT view showing thinning of the outer retina. The pedigree shows pseudodominant (autosomal recessive) inheritance, seen in consanguineous families though consanguinity is not documented. The family was not available for segregation analysis. (V) Proband 5: (a) Imaging of the retina showing retinal atrophy outside the central area (macula) but the vessels were not severely constricted. bone spicules were visible only in the periphery (not shown). (b) OCT imaging showing thinning of the outer retina. c) Normal chest X-ray (AP view). The family pedigree is shown with segregation of variants with the phenotype. (VI) Normal OCT showing the different layers of the retina. Important to this work is the outer retina, which includes CL connecting cilia layer, ISL inner segment layer, OSL outer segment layer, RPE/BM retinal pigment epithelium/Bruch’s membrane, WT wild type.