Case#: 80 yo M, siagonosed at 18 yo

DiseaseAssertion: Stargardt

FamilyInfo: one of his 2 sisters had same mutation to ABCA4

CasePresentingHPOs:,HP:0007663, HP:0008002

CaseHPOFreeText: RPE hyperplasia, atrophy of the inner and outer photoreceptor segments, the outer nuclear layer, and the outer plexiform layer, with scanty RPE cells in the macular area

CaseNotHPOs: NA

CaseNotHPOFreeText: NA

Genotyping Method: N/A

PreviouslyPublished: none

Variant: G1961E

ClinVar: 7888

SupplementalData: See supplemental Material for further look at the probands Human Embryonic Stem Cell-derived Retinal Pigment Epithelium Transplantation

Case#: patient, 11, Somali, onset 8yo

DiseaseAssertion: STGD

FamilyInfo: parents and four siblings did not report visual issues

CasePresentingHPOs: HP:0000007, HP:0011504, HP:0000608

CaseHPOFreeText: BCVA 20/70 OD, 20/80 OS. Bull's eye maculopathy. Outer retinal and RPE atrophy. Slight opacity at level of RPE; loss of outer retinal structures in central area. Normal peripheral retina.

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: whole genome

PreviouslyPublished: PMID:28559085

Variant: NM_000350.3:c.5882G>A p.(Gly1961Glu) ; NM_000350.3:c.634C>T p.(Arg212Cys)

ClinVar:7888; 7898

CAID:n/a

SupplementalData:n/a

Case#: patient, 12, Somali, onset 5yo

DiseaseAssertion: STGD

FamilyInfo: parents and 5 siblings did not report visual issues

CasePresentingHPOs: HP:0000007, HP:0011504, HP:0000608

CaseHPOFreeText: BCVA 20/135 OD; 20/100 OS. Red-green color deficit. Bull's eye maculopathy, but no pallor of optic disc. Normal peripheral retina. Loss of macular photoreceptor layer; severely reduced cone function.

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: whole exome sequencing

PreviouslyPublished: n/a

Variant: NM_000350.3:c.5882G>A p.(Gly1961Glu) ; NM_000350.3:c.634C>T p.(Arg212Cys)

ClinVar: 7888; 7898

CAID: n/a

SupplementalData: n/a

Case#:5-year-old girl

DiseaseAssertion: Asymptomatic

FamilyInfo: Mother was diagnosed with STGD1 and She was homozygous for a (severe) splice site mutation, IVS 35+2 T>C, Maternal uncle was diagnosed with STGD1. Father passed down the G1961E variant.

CasePresentingHPOs: HP:0030630, HP:0011504

CaseHPOFreeText: The ELM in the central macula appeared thickened with indistinct borders, particularly along its inner border (Fig. 2C), horizontal diameter for the region of thickened ELM was 1113 μm, FAF revealed Bull’s Eye Maculopathy (BEM) (Fig. 2B),

CaseNotHPOs:

CaseNotHPOFreeText: No retinal, vasculature, pigmentary or optic nerve head abnormalities were detected on clinical examination, no focal abnormality observed in the outer nuclear layer (ONL) or RPE (Fig. 2C), There was no FAF evidence of flecks or GA

Genotyping Method:

PreviouslyPublished: No

Variant:NM_000350.3:c.5882G>,

ClinVar:7888

CAID:CA119132

SupplementalData:

Case#: Patient 1, male, Caucasian, onset at 20yo, USA

DiseaseAssertion: ABCA4

FamilyInfo: No family history of retinal disease.

CasePresentingHPOs: HP:0007677, HP:0030603, HP:0030500, HP:0030636, HP:0004328, HP:0012372

CaseHPOFreeText: Bilateral central vision loss, progressive decline in visual acuity (20/60 both eyes), foveomacular vitelliform lesions with fluid accumulation, optical gap lesions progressing to cavitated appearance after fluid resorption, thinning and abnormal reflectivity of photoreceptor layers, near-infrared autofluorescence abnormalities in lesion-adjacent regions

CaseNotHPOs: HP:0000510, HP:0000511

CaseNotHPOFreeText: No generalized rod or cone dysfunction on full-field electroretinogram, EOG findings not consistent with bestrophinopathy (Arden ratio 1.62)

Genotyping Method: Exome sequencing

PreviouslyPublished: None

Variant: NM_000350.3(ABCA4):c.5882G>A (p.Gly1961Glu), NM_000350.3(ABCA4):c.4139C>T (p.Pro1380Leu)

ClinVar: ClinVarID:7888, ClinVarID:7904

CAID: N/A

SupplementalData: N/A

Case#: 1 male, 24 years old, from consanguineous parents, Somali ancestry.

DiseaseAssertion: ABCA4-related retinopathy Stargardt disease

FamilyInfo: Single affected individual consanguineous parents, Somali ancestry. No additional information about family is provided in text.

CasePresentingHPOs: HP:0000572- reduced central vision, HP:0001102- Angioid streaks, HP:0007980- retinal pigment epithelium atrophy, HP:0007401- Macular atrophy, HP:0000630- Abnormal retinal arterial/arteriolar morphology

CaseHPOFreeText: Presents with reduced central vision, Fundus autofluorescence (FAF) showed angioid streaks, reduced signal in the central macula indicative of retinal pigment epithelium atrophy. Electrophysiological testing showed severe macular dysfunction with generalized retinal involvement.

CaseNotHPOs: HP:0200070- Peripheral retinal atrophy

CaseNotHPOFreeText: Peripheral retina appears unaffected after ultra-widefield FAF imaging

Genotyping Method: PCR-amplification and Sanger sequencing of ABCA4 on Exon 42, Stargardt/Macular dystrophy SmartPanel v5; Molecular Vision Laboratory, Hillsboro, Oregon tested DNA for mutations which confirmed findings of ABCA4, with no additional pathogenic mutations found.

PreviouslyPublished: PMID: 22261738, 1 male, 24 years old, from consanguineous parents, Somali ancestry presenting with reduced vision.

Variant: NM_000350.3(ABCA4):c.5882G>A (p.Gly1961Glu)

ClinVar: Variation ID: 7888

CAID: N/A

SupplementalData: N/A

Case#:3, 34–year-old woman

DiseaseAssertion:NR

FamilyInfo: no family history of an ocular disease

CasePresentingHPOs: HP:0007663, HP:0030506, HP:0030528, HP:0000603

CaseHPOFreeText:bilateral markedly decreased vision (logMar BCVA OD:0.93, OS:0.95), bilateral atrophic lesions of the macula accompanied by yellow-white stellate flecks at the level of the retinal pigment epithelium, Atrophic lesions and flecks were also extending to the mid-periphery of both retinae, bilateral absolute central scotoma and relative paracentral scotomas as well in both eyes, PERG was significantly reduced, while scotopic and photopic amplitudes were also lower than normal.

CaseNotHPOs:

CaseNotHPOFreeText:NR

Genotyping Method: “Analysis of the ABCA4 gene”

PreviouslyPublished: No

Variant: NM_000350.3:c.5882G>A, NM_000350.3:c.6709dup

ClinVar: ​​7888, 99485

CAID: CA119132, CA227437

SupplementalData:

Case#:48-year old man, onset at 13-years old

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs: HP:0003621, HP:0025147, HP:0011507, HP:0030329, HP:0030610, HP:0007722, HP:0007703, HP:0007663

CaseHPOFreeText: BCVA was 20/200 bilaterally and refractive error was OD: −1.50/+0.50 × 149° and OS: −1.50/+0.25 × 161°. Hyperautofluorescent transitional zone in each eye more pronounced in right eye. The left eye showed a complete defect of the RPE-Bruch membrane complex with herniation of the outer retina. Maximum horizontal diameter of this RPE-Bruch membrane complex defect was 266um.

CaseNotHPOs: HP:0000510, HP:0000548, HP:0007984

CaseNotHPOFreeText: No defect observed in the RPE and Bruch membrane in right eye. Patient had normal cone and rod responses on ERG

Genotyping Method: ABCR 600 micro-array chip

PreviouslyPublished: n/a

Variant: NM_000350.3(ABCA4):c.4216C>T (p.His1406Tyr), NM_000350.3(ABCA4):c.5882G>A (p.Gly1961Glu)

ClinVar: 99259, 7888

SupplementalData: n/a

Case#: 1 female, 12 years old.

DiseaseAssertion: bilateral stage 2B Coats disease. ABCA4 gene mutations were found upon genetic analysis but Stargardt disease was not diagnosed.

FamilyInfo: Single affected individual. Past medical history and family history was reported as normal. No additional information about family is provided in text.

CasePresentingHPOs: HP:0007663 - Reduced visual acuity, HP:0001147 - Retinal exudate, HP:0007763 - Retinal telangiectasia, HP:0025355 - Retinal arteriolar macroaneurysms, HP:0011505- Cystoid macular edema, HP:0020032 - Hyperreflective retinal dots on OCT, HP:0001045 - Vitiligo

CaseHPOFreeText: bilateral significant capillary nonperfusion noted mostly in the temporal retinal periphery together with light-bulb-like capillary dilations and staining of telangiectatic vessels. Mild intravitreal hemorrhage

CaseNotHPOs: HP:0012045 - Retinal flecks, HP:0025010 - Foveal atrophy, HP:0000603 - Central scotoma, HP:0000556 - Retinal dystrophy, HP:0000512 - Abnormal electroretinogram

CaseNotHPOFreeText: Relatively normal foveal architecture.

Genotyping Method: Genetic analysis was performed using Sanger sequencing for the NDP gene, which revealed no pathogenic variants. Exome sequencing was then used with the Illumina HiSeq 2500 platform, which identified two compound heterozygous variants in the ABCA4 gene. Lastly, no mutations were found in the TINF2 gene.

PreviouslyPublished: N/A

Variant: NM_000350.3(ABCA4):c.1373C>T (p.Arg458Cys), NM_000350.3(ABCA4):c.5882G>A (p.Gly1961Glu)

ClinVar: Variation ID: 7888 ( for p.Arg458Cys variant however I believe this is mislabeled for this variant NM_000350.3(ABCA4):c.5882G>A (p.Gly1961Glu), no variantion ID found for NM_000350.3(ABCA4):c.1373C>T (p.Arg458Cys)

CAID: N/A

SupplementalData: N/A