Case#: P10-GR, F, Age of Report: 63 y.o., Ethnicity: Greece.

CasePresentingHPOs: HP:0000662 (Nyctalopia), HP:0001133 (Constriction of peripheral visual field), HP:0000613 (Photophobia), HP:0200070 (Peripheral retinal atrophy/diffuse outer retinal atrophy), HP:0025010 (Foveal atrophy), HP:0500087 (Peripapillary atrophy), HP:0030329 (Retinal thinning), HP:0008619 (Bilateral sensorineural hearing impairment/bilateral hearing impairment/moderate SNHL)

CaseHPOFreeText: P10-GR is a 63 year-old female with adulthood-onset RP. She is the third offspring of a non-consanguineous marriage with no family history of RP or hearing loss (Fig.1g).

She reported night blindness since the age of 25 years with subsequent visual field constriction around the age of 35 and recent onset of photophobia. Her BCVA was 0.16 D in the right eye and 0.125 D in the left eye and she was pseudophakic. Fundoscopy revealed the presence of diffuse outer retinal atrophy with intraretinal pigment migration in the mid- and far-periphery along with foveal and peripapillary atrophy and vessel attenuation. FAF imaging showed areas of hypo-autofluorescence in the periphery, around the optic disc and in the fovea corresponding to the areas of retinal atrophy. SD-OCT showed retinal thinning with atrophy of outer retinal layers and foveal RPE loss (Fig. 2f, Table 2). The patient reported bilateral hearing impairment since the age of 58 years. Audiometry confirmed the presence of moderate SNHL with a flat audiogram and a PTA of 50 dB (Fig. 3).

CaseNotHPOs: N/A..

CaseNotHPOFreeText: N/A.

CasePreviousTesting: N/A.

CaseMethod1: N/A

CaseMethod2: N/A.

CaseGenotypingMethod: WES.

Variant: Variant 1: NM_021831.6:c.883G>A (p.Asp295Asn). Variant 2: NM_021831.6:c.316A>G (p.Met106Val ).

ClinVar: Variant 1: 242932. Variant 2: N/A.

CAID: Variant 1: CA10584033. Variant 2: CA346170014.

gnomAD: Variant 1: Frequency: 0.000005530. Link: https://gnomad.broadinstitute.org/variant/chr2-27055228-G-A?dataset=gnomad_r4. Variant 2: Frequency: 6.800e-7. Link: https://gnomad.broadinstitute.org/variant/chr2-27053502-A-G?dataset=gnomad_r4.

VariantEvidence: N/A.

CaseAddInfo: Molecular analysis identified two compound heterozygous variants in AGBL5: c.883G>A, p.(Asp295Asn) and c.316A>G, p.(Met106Val), that were shown to be in trans, since the unaffected daughter of the patient only carries the c.883G>A, p.(Asp295Asn) (Fig. 1g, Table 1).

CasePMIDs: N/A.