Case#: 32-year old woman, onset in early twenties

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs: HP:0011462, HP:0011507, HP:0000505, HP:0007722, HP:0030500, HP:0030329, HP:0030610, HP:0000575, HP:0030602

CaseHPOFreeText: Patient’s best-corrected visual acuity was OD: 20/200 and OS: 20/40. Refractive error was OD: −5.25/−0.75 × 4° and OS: −5.75/−0.50 × 133°. Flecks in macular area extended anterior to the vascular arcades and the optic disc in both eyes. Atrophic lesion in the macula with flecks observed across the posterior pole. IS/OS junction loss central macular area bilaterally. Absolute scotoma in left eye (ie total deviation −20 dB). Defect in the RPE/Bruch membrane complex was observed on SD-OCT in both eyes in the central macula. The defects in the RPE-Bruch membrane complex measured OD: 332 um and OS: 266 um in maximum horizontal diameter. Herniation of the retina through these defects into the sub-RPE/choroidal space. Abnormal thickening of the RPE in the parafoveal region. Normal amplitudes and implicit times in both rod and cone photoreceptor systems were detected by ERG.

CaseNotHPOs: HP:0000510, HP:0007984

CaseNotHPOFreeText: Normal amplitudes and implicit times in both rod and cone photoreceptor systems were detected by ERG. There was no evidence of sub-RPE choroidal neovascularization (CNV), pigment epithelial defects (PED) or subretinal fluid.

Genotyping Method: ABCR 600 micro-array chip

PreviouslyPublished: n/a

Variant: NM_000350.3(ABCA4):c.5714+5G>A

ClinVar: 99403

SupplementalData: n/a

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#: Male, mid-40s

DiseaseAssertion: STGD1

FamilyInfo: Retinal disease reported in sibling and material grandfather. Mother exhibited decreased visual acuity, BEM in right eye, and tapetal reflex in both eyes.

CasePresentingHPOs: HP:0000622, HP:0000613, HP:0000662, HP:0011504, HP:0007663, HP:0011463

CaseHPOFreeText: n/a

CaseNotHPOs: HP:0007843, HP:0011507

CaseNotHPOFreeText: Autofluorescence(qAF): 381.5. The Case's qAF was noted to be in the range observed in healthy eyes, and also lower than many other STGD1 patients with the same age. There were no flecks, intraretinal pigment migration, retinal vessel attenuation, or optic nerve pallor (Figure 1).

Genotyping Method: Sanger Sequencing

PreviouslyPublished: n/a

Variant: NM_000350.3(ABCA4):c.1411G>A (p.Glu471Lys), NM_001034853.2(RPGR):c.3070G>T (p.Glu1024Ter)

ClinVar: 99052, 1275798

SupplementalData: n/a

Case#: Patient 66yo, M, Japan, Symptoms in teens

DiseaseAssertion: Stargardt (STGD) Heterozygous, Autosomal recessive

FamilyInfo: No family with similar symptoms

CasePresentingHPOs: HP:0008002, HP:0007722, HP:0000610, HP:0000602

CaseHPOFreeText: Ring shaped paracentral scotoma

CaseNotHPOs: HP: 0030329, HP:0000608, HP:0000493

CaseNotHPOFreeText: Well preserved foveal function, well preserved retinal, and normal thickness RPE

Genotyping Method: N/A

PreviouslyPublished: 4 other polymorphisms

Variant: c.839T>C p.Met280Thr Heterozygous

ClinVar: 1349490

SupplementalData: see tables 1 for gene variant and found polymorphisms

Case#: 43-year old man, German descent, onset within first decade of life

DiseaseAssertion: STGD1

FamilyInfo: Family pedigree shown in Figure 1.

CasePresentingHPOs: HP:0011463, HP:0000533, HP:0000580, HP:0030500, HP:0011507, HP:0000548, HP:0000510, HP:0007703, HP:0007663, HP:0000512, HP:0000610

CaseHPOFreeText: Retinal vessels were visibly attenuated.

CaseNotHPOs: n/a

CaseNotHPOFreeText: Peripapillary region around the optic nerve had no disease related changes.

Genotyping Method: Illumina MiSeq platform, Array-CGH analysis

PreviouslyPublished: n/a

Variant: NM_000350.3(ABCA4):c.161G>A (p.Cys54Tyr), NM_000350.3(ABCA4):c.4539+2028C>T

ClinVar: 99065, 236116

SupplementalData: n/a

Case#: Patient 66yo, M, Japan, Symptoms in teens

DiseaseAssertion: Stargardt (STGD) Heterozygous, Autosomal recessive

FamilyInfo: No family with similar symptoms

CasePresentingHPOs: HP:0008002, HP:0007722, HP:0000610, HP:0000602

CaseHPOFreeText: Ring shaped paracentral scotoma

CaseNotHPOs: HP: 0030329, HP:0000608, HP:0000493

CaseNotHPOFreeText: Well preserved foveal function, well preserved retinal, and normal thickness RPE

Genotyping Method: N/A

PreviouslyPublished: 4 other polymorphisms

Variant: c.839T>C p.Met280Thr Heterozygous

ClinVar: 1349490

SupplementalData: see tables 1 for gene variant and found polymorphisms

Case#: Patient female, 48y, ethnicity not reported

DiseaseAssertion: Stargardt disease (STGD1) with unusual phenotype resembling pattern dystrophy

FamilyInfo: autosomal recessive inheritance; segregation analysis confirms each parent carries one variant (heterozygous). Pedigree shown in Figure 3. Proband is compound heterozygous for ABCA4 variants.

CasePresentingHPOs: HP:0007663, HP:0007754, HP:0030636, HP:0000548

CaseHPOFreeText: mild visual impairment (BCVA 20/25 and 20/20), perifoveal yellow fleck-like lesions, hyperautofluorescent lesions with lipofuscin accumulation, foveal sparing, subretinal material accumulation, phenotype resembling pattern dystrophy, bilateral macular involvement, decreased p50 values on pattern ERG

CaseNotHPOs: HP:0000510 (normal ERG responses except pattern ERG component)

CaseNotHPOFreeText: normal full-field ERG (scotopic and photopic responses), normal electrooculography, preserved outer retina structure, minimal photoreceptor disruption at fovea

Genotyping Method: targeted next-generation sequencing (Illumina NextSeq500) with SeqCap EZ enrichment panel; Sanger sequencing used for confirmation and segregation analysis

PreviouslyPublished: n/a

Variant: ABCA4 NM_000350.2: c.428C>T (p.Pro143Leu); c.3113C>T (p.Ala1038Val)

ClinVar: 99273; 7894

CAID: n/a

SupplementalData: clinical imaging and genetic/segregation data in supplemental data (Figures 1–3, Table 1)

Case#: 25-year old female, juvenile onset

DiseaseAssertion: STGD1

FamilyInfo: Figure 1 shows family pedigree. Table 1 shows clinical features of a Chinese pedigree. Cosegregation analysis was done and shown in Figure 1A, C.

CasePresentingHPOs: HP:0007663, HP:0007722, HP:0007401, HP:0030329, HP:0030610, HP:0003621, HP:0011507, HP:0007984

CaseHPOFreeText: The uncorrected visual acuity of each eye was 20/400, which has progressively decreased for 13 years.

CaseNotHPOs: n/a

CaseNotHPOFreeText: The retinal vessels were normal.

Genotyping Method: Whole Exome Sequencing, Sanger Sequencing

PreviouslyPublished: n/a

Variant: NM_000350.3(ABCA4):c.3523-2A>G, NM_000350.3(ABCA4):c.5646G>A (p.Met1882Ile)

ClinVar: 866764, 377407

SupplementalData: n/a

Case#: Patient 37 yo, F, Eastern Asian, onset at 8yo (early onset), Heterozygous, AR inheritance patterns

DiseaseAssertion:Retinitis Pigmentosa (RP)

FamilyInfo: Two brothers with RP and father with poor vision at 30 yo but no formal diagnosis

CasePresentingHPOs: HP:0003581, HP:0007737, HP:0000510, HP:000133

CaseHPOFreeText: N/A

CaseNotHPOs: HP: 0000007, HP:0007663, HP:0000505, HP:0000662

CaseNotHPOFreeText: N/A

Genotyping Method: N/A

PreviouslyPublished: Panel of genes; RP1L1, RP-GRIP1, ABCA4, and GRM6

Variant: c.5501T>C p.(Met1019Ille)

ClinVar: 1481089

SupplementalData: see tables 1 and 2 for genetic variant panel