Case: Gustafson_II:3

CasePresentingHPOsFreeText: Retrospective review of ophthalmic examination notes was performed in three affected family members (II:2, II:4, and II:6). Information about eye examination, including best corrected visual acuity (BCVA) and dilated fundus examination, kinetic perimetry, and spectral-domain optical coherence tomography (SD-OCT) scans through the fovea were obtained in all three affected patients (Spectralis HRA+OCT, Heidelberg Engineering, Heidelberg, Germany and Cirrus HD OCT, Carl Zeiss Meditech Inc., Dublin, CA, USA). Full-field electroretinogram (ERG) testing was performed according to International Society for Clinical Electrophysiology of Vision (ISCEV) standards [ 4 ] in the two sisters (II:2 and II:4) but was not performed in the second cousin (II:6).

CasePreviousTesting: WES

CaseGenotypingMethod: Whole exomes of three affected (II:2, II:4 and II:6) and to unaffected family members (I:6, II:3) were sequenced using Agilent Sure Select V1 probes (Agilent Technologies, Inc., Santa Clara, CA, USA) and Illumina HiSeq 2500 (Illumina, San Diego, CA, USA). Whole genomes of family members II:2, II:3, II:4, II:6, and I:6 were sequenced at more than 30X depth using Illumina HiSeq X (Illumina,). Segregation of substitution mutations and small deletions were tested by dideoxy sequencing

Variant: c.226C>T (p.Arg76*)

ClinVarID: or CAID: CA151548

gnomAD: allele freq. of 0.001173 in the Latino population

AddCaseInfo: Ashkenazi Jewish

PreviouslyPublished:

VariantEvidence:

Case: Gustafson_II:1, female, 60 years old

CasePresentingHPOsFreeText: Retrospective review of ophthalmic examination notes was performed in three affected family members (II:2, II:4, and II:6). Information about eye examination, including best corrected visual acuity (BCVA) and dilated fundus examination, kinetic perimetry, and spectral-domain optical coherence tomography (SD-OCT) scans through the fovea were obtained in all three affected patients (Spectralis HRA+OCT, Heidelberg Engineering, Heidelberg, Germany and Cirrus HD OCT, Carl Zeiss Meditech Inc., Dublin, CA, USA). Full-field electroretinogram (ERG) testing was performed according to International Society for Clinical Electrophysiology of Vision (ISCEV) standards [ 4 ] in the two sisters (II:2 and II:4) but was not performed in the second cousin (II:6)

CasePreviousTesting: WES

CaseGenotypingMethod: Whole exomes of three affected (II:2, II:4 and II:6) and to unaffected family members (I:6, II:3) were sequenced using Agilent Sure Select V1 probes (Agilent Technologies, Inc., Santa Clara, CA, USA) and Illumina HiSeq 2500 (Illumina, San Diego, CA, USA). Whole genomes of family members II:2, II:3, II:4, II:6, and I:6 were sequenced at more than 30X depth using Illumina HiSeq X (Illumina,). Segregation of substitution mutations and small deletions were tested by dideoxy sequencing

Variant: c.226C>T (p.Arg76*)

ClinVarID: or CAID: CA151548

gnomAD: allele freq. of 0.001173 in the Latino population

AddCaseInfo: Ashkenazi Jewish

PreviouslyPublished:

VariantEvidence:

Case: Shamieh_FamilyC_II:3; CIC01225

CasePresentingHPOsFreeText: Rod-cone dystrophy, Each subject underwent an ophthalmic exami- nation with clinical assessment as previously described. The three affected individuals with KIZ variants in this study were all diagnosed with RCD in their late teens on the basis of night blindness followed by changes in mid- peripheral visual fields and undetectable responses in a full-field electroretinogram by approximately 35 years of age.

CasePreviousTesting: No mention of previous testing

CaseGenotypingMethod: screening of coding and flanking exonic regions of KIZ by direct Sanger sequencing

Variant: compound heterozygous for the c.52G>T (p.Glu18) and c.119_122delAACT (p.Lys40Ilefs14) variants.

ClinVarID: or CAID: c.52G>T (CA151550) , c.119_122delAACT (CA151553)

gnomAD: allele frequency = 0.00009237 for the c.119_122delAACT variant, c.52G>T variant is absent from gnomAD v2.1.1

AddCaseInfo: Cosegregation analysis revealed that the father was heterozygous for the nonsense mutation and the mother was heterozygous for the frameshift deletion

Case: Jauregui_Case3

CasePresentingHPOsFreeText: The data presented in this study, including images and genetic testing results, is not identifiable to individual patients. A retro- spective review of patients with a clinical diagnosis of RP by an inherited retinal disease specialist (SHT) at the Department of Ophthalmology at Columbia University was conducted. The clinical diagnosis was based on pre- senting symptoms, family history, fundus examination, and subsequently supported by clinical imaging, full-field electroretinography (ffERG), and/or genetic testing. Ophthalmic examinations included a slit-lamp and dilated funduscopic examination, best-corrected visual acuity (BCVA), short-wavelength fundus autofluorescence (SW- AF, 488 nm excitation), and spectral domain optical coherence tomography (SD-OCT). The inclusion criteria for this study were the diagnosis of RP and genetic characterization of the disease, while the exclusion criteria precluded monocular patients or those without SD-OCT or SW-AF imaging

CasePreviousTesting: not mentioned

CaseGenotypingMethod: not mentioned

Variant: c.226C>T (p.R76X)

ClinVarID: or CAID: CA151548

gnomAD: allele freq. of 0.001173 in the Latino population

AddCaseInfo: Male. Caucasian, 21 years old

PreviouslyPublished:

VariantEvidence:

Case: Jauregui_Case2

CasePresentingHPOsFreeText: The data presented in this study, including images and genetic testing results, is not identifiable to individual patients. A retro- spective review of patients with a clinical diagnosis of RP by an inherited retinal disease specialist (SHT) at the Department of Ophthalmology at Columbia University was conducted. The clinical diagnosis was based on pre- senting symptoms, family history, fundus examination, and subsequently supported by clinical imaging, full-field electroretinography (ffERG), and/or genetic testing. Ophthalmic examinations included a slit-lamp and dilated funduscopic examination, best-corrected visual acuity (BCVA), short-wavelength fundus autofluorescence (SW- AF, 488 nm excitation), and spectral domain optical coherence tomography (SD-OCT). The inclusion criteria for this study were the diagnosis of RP and genetic characterization of the disease, while the exclusion criteria precluded monocular patients or those without SD-OCT or SW-AF imaging

CasePreviousTesting: not mentioned

CaseGenotypingMethod: not mentioned

Variant: c.226C>T (p.R76X)

ClinVarID: or CAID: CA151548

gnomAD: allele freq. of 0.001173 in the Latino population

AddCaseInfo: Male. Caucasian, 60 years old

PreviouslyPublished:

VariantEvidence:

Case: Jauregui_Case1

CasePresentingHPOsFreeText: The data presented in this study, including images and genetic testing results, is not identifiable to individual patients. A retro- spective review of patients with a clinical diagnosis of RP by an inherited retinal disease specialist (SHT) at the Department of Ophthalmology at Columbia University was conducted. The clinical diagnosis was based on pre- senting symptoms, family history, fundus examination, and subsequently supported by clinical imaging, full-field electroretinography (ffERG), and/or genetic testing. Ophthalmic examinations included a slit-lamp and dilated funduscopic examination, best-corrected visual acuity (BCVA), short-wavelength fundus autofluorescence (SW- AF, 488 nm excitation), and spectral domain optical coherence tomography (SD-OCT). The inclusion criteria for this study were the diagnosis of RP and genetic characterization of the disease, while the exclusion criteria precluded monocular patients or those without SD-OCT or SW-AF imaging

CasePreviousTesting: not mentioned

CaseGenotypingMethod: not mentioned

Variant: c.119_122delAACT (p.K40IfsX14)

ClinVarID: or CAID: CA151553

gnomAD: allele freq. of 0.00009237 in the European (non-finnish) population

AddCaseInfo: Male. Caucasian, 56 years old

PreviouslyPublished:

VariantEvidence:

Case: Lin_FamilyB_II:1

CasePresentingHPOsFreeText: Ophthalmic examination notes were retrospectively reviewed in patients. Best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus examination, spectral-domain optical coherence tomography (SD-OCT) scans through the fovea, and short-wavelength fundus autofluorescence (SW-AF, 488 nm), were obtained in all four affected patients with Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany). Full-field electroretinogram (ERG) testing was performed according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. The patients in this study exhibited chorioretinal phenotypes characteristic of RP (Figure 1). All patients initially presented with night blindness followed by progressive constriction of their visual field. ERG recordings were collected from three patients (A-II:2, B-II:1, and D-II:5) (Figure 3). For A-II:2 at 60 years of age and D-II:5 at age 37 years of age, ERG rod responses of the right eyes were almost undetectable.

CasePreviousTesting: WES

CaseGenotypingMethod: Genetic testing was performed in all four patients in this study, using either whole exome sequencing (WES, A-II:2, B-II:1, and D-II:5)

Variant: c.119_122delAACT (p.Lys40llefsTer14)

ClinVarID: or CAID: CA151553

gnomAD: allele frequency of 0.00009237 in the European (non-Finnish) population

AddCaseInfo:

PreviouslyPublished:

VariantEvidence:

Case: Lin_FamilyD_II:5

CasePresentingHPOsFreeText: Ophthalmic examination notes were retrospectively reviewed in patients. Best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, fundus examination, spectral-domain optical coherence tomography (SD-OCT) scans through the fovea, and short-wavelength fundus autofluorescence (SW-AF, 488 nm), were obtained in all four affected patients with Spectralis HRA+OCT (Heidelberg Engineering, Heidelberg, Germany). Full-field electroretinogram (ERG) testing was performed according to the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. The patients in this study exhibited chorioretinal phenotypes characteristic of RP (Figure 1). All patients initially presented with night blindness followed by progressive constriction of their visual field. ERG recordings were collected from three patients (A-II:2, B-II:1, and D-II:5) (Figure 3). For A-II:2 at 60 years of age and D-II:5 at age 37 years of age, ERG rod responses of the right eyes were almost undetectable.

CasePreviousTesting: WES

CaseGenotypingMethod: Genetic testing was performed in all four patients in this study, using either whole exome sequencing (WES, A-II:2, B-II:1, and D-II:5)

Variant: c.226C>T (p.Arg76Ter)

ClinVarID: or CAID: CA151548

gnomAD: allele frequency of 0.001173 in the Latino population

AddCaseInfo:

PreviouslyPublished:

VariantEvidence: