Case#: Patient 10, female, age 19

DiseaseAssertion: STGD

FamilyInfo: diagnosis of autosomal recessive STGD based on the pedigree and clinical phenotype of fleck deposits with or without genetic testing

CasePresentingHPOs: HP:0000608, HP:0000007, HP:0030610, HP:0030500

CaseHPOFreeText: Macular degeneration. autosomal recessive, Photoreceptor outer segment loss on macular OCT, Yellow/white lesions of the macula

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: n/a

PreviouslyPublished: n/a

Variant: Allele 1: NM_000350.3:c.2588G>C Allele 2: NM_000350.3:c.1222C>T

ClinVar: Allele 1: NM_000350.3(ABCA4):c.2588G>C (p.Gly863Ala) Allele 2: NM_000350.3(ABCA4):c.1222C>T (p.Arg408Ter)

CAID: Allele 1: CA119128 Allele 2: CA179692

SupplementalData: composite mask analysis shown in figure 3 for patient 10

PMID: 30771335

Gene: ABCA4

HGNC ID: 34

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#: 12, Somali, onset 5 years old

DiseaseAssertion: STGD

FamilyInfo: Parents were heterozygous for Arg212Cys, no family history of IRD

CasePresentingHPOs: HP:0011504, ORPHA:827, HP:0000608

CaseHPOFreeText: Bull's eye maculopathy, macular degredation, red-green color defecit, reduced cone function

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: Whole exome sequencing

PreviouslyPublished: N/a

Variant:

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

ClinVar: 7888; 7898

CAID: CA119132, CA203216

SupplementalData: N/a

PMID: 41063816 Gene:ABCA4 HGNC:34

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#: DNAID 071549/Pat23, male

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: "In classic STGD1, loss of central vision starts around the second decade of life, but both early- and late-onset subtypes have been extensively described." No patient-specific details provided

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: smMIPs sequencing of the complete ABCA4 locus

PreviouslyPublished: n/a

Variant: c.6416G>C (p.Arg2139Pro); c.1648G>A (p.Gly550Arg)

CAID: CA10611614

SupplementalData: tables s9 and s11

Case#: DNAID 072884/Pat255, female

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: "In classic STGD1, loss of central vision starts around the second decade of life, but both early- and late-onset subtypes have been extensively described." No patient-specific details provided

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: smMIPs sequencing of the complete ABCA4 locus

PreviouslyPublished: n/a

Variant: c.1519G>T (p.Asp507Tyr); c.5312+3A>T (p.Asn1734Glyfs*14) phase not confirmed

CAID: CA958508

SupplementalData: tables s9 and s11

PMID: 37705246

Gene: ABCA4

Disease: ABCA4-associated retinopathies

Case#: 43 year old woman II:2

DiseaseAssertion: Stargardt disease (STGD1)

FamilyInfo: none of family had co-existing systemic disorders, father carried variant, probands affected suster did not

CasePresentingHPOs:HP:0000007

CaseHPOFreeText: loss of ellipsoid zone, mascular dystrophy with features of bull's eye maculopathy,

CaseNotHPOs: na

CaseNotHPOFreeText: na

Genotyping Method: sanger sequencing

PreviouslyPublished: n/a

Variant: c.4685 T > C, p.(I1562T)

ClinVar: not found

CAID: not found

SupplementalData: probands affected sister did not carry the ABAA4 variant, indicating ABCA4 was not relevant to mascular dystrophy in family, CRX variant was also found

Case#: Proband P399, Family F345, male, 8yo at onset, US

DiseaseAssertion:

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: phenotypically focused tiered testing strategy beginning with allele-specific testing of the most common disease alleles and progressing through Sanger sequencing of candidate genes and, in many cases, to next generation sequencing of whole exomes and whole genomes

PreviouslyPublished: n/a

Variant: Pro1380Leu (c.4139C>T); Glu2031Lys (c.6091G>A) phase unconfirmed

ClinVar: 866538

CAID: CA341279017

SupplementalData: table s2 (listed as table 1 when you open it)

Case#: MD-0170 Proband, 14yo at onset

DiseaseAssertion: STGD

FamilyInfo: Family MD-0170

CasePresentingHPOs:

CaseHPOFreeText: STGD diagnosed based on "bilateral central vision loss; fundus presenting with a beaten-bronze appearance and/or the presence of orange-yellow flecks in the retina from the posterior pole to the mid-periphery; fluorescein angiography showing typical dark choroid; and normal to subnormal electroretinogram (ERGs)."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Haplotype analysis, ABCR400

PreviouslyPublished: unclear

Variant: c.4457C>T (p.Pro1486Leu); c.1222C>T (p.Arg408*)

ClinVar: 99283

CAID: CA227192

SupplementalData: n/a

Case#: Family MD-0084 Proband, 7yo at onset

DiseaseAssertion: AR Stargardt

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: STGD diagnosed based on "bilateral central vision loss; fundus presenting with a beaten-bronze appearance and/or the presence of orange-yellow flecks in the retina from the posterior pole to the mid-periphery; fluorescein angiography showing typical dark choroid; and normal to subnormal electroretinogram (ERGs)." VA loss, VF loss, BCVA=<0.05/<0.05

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: PMID: 16917483 (variant not found in this paper); PMID: 19959634

Variant: c.6410G>A (p.Cys2137Tyr) homozygous, found by ABCR400 + dHPLC + HRM + MLPA

ClinVar: 2202779

CAID: CA341277358

SupplementalData:

Case#: Family MD-0242 Proband, 18yo at onset, Spanish

DiseaseAssertion: AR Stargardt

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: STGD diagnosed based on "bilateral central vision loss; fundus presenting with a beaten-bronze appearance and/or the presence of orange-yellow flecks in the retina from the posterior pole to the mid-periphery; fluorescein angiography showing typical dark choroid; and normal to subnormal electroretinogram (ERGs)."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Haplotype analysis, ABCR400 microarray, direct sequencing for confirmation

PreviouslyPublished: n/a

Variant: c.1715G>C p.Arg572Pro

ClinVar: 99073

CAID: CA226919

SupplementalData:

Case#: Fishman Patient #22, male, 28yo

DiseaseAssertion: Stargardt dystrophy or fundus flavimaculatus

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: dark choroid, diffuse yellowish white flecks in the fundus, 20/400 OU, central scotoma

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: only one variant found: c.6383A>G (p.His2128Arg) Single-strand conformation polymorphism analysis and DNA sequencing were used to identify variations in coding sequences of the ABCRgene.

ClinVar: 99455

CAID: CA227399

SupplementalData:

Case#: Patient#010046, Chinese, 28yo at onset

DiseaseAssertion: stargardt

FamilyInfo: n/a

CasePresentingHPOs: STGD1 diagnosis based on the following criteria: "a bilateral central vision defect; fundus displaying a beaten-bronze appearance and/or orange-yellow flecks in the retina from the macula to the midperiphery; fluorescein angiography presenting with a typical dark choroid; and normal to subnormal ERG results." stage 2( numerous yellow-whitish flecks throughout the posterior pole) BCVA=0.05/ 0.05

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: p.P2097S; p.A1773V phase unknown

ClinVar: 2202780

CAID: CA341277622

SupplementalData: supplementary table S3 has phenotype information

PMID: 26780318

Gene: ABCA4

Disease: Stargardt Disease or Cone-Rod Dystrophy

Case#: STGD138, 15-19yo at onset, German

DiseaseAssertion: STGD

FamilyInfo: segregation in family

CasePresentingHPOs:

CaseHPOFreeText: "The diagnosis of STGD was based on the demonstration of bilateral impairment of central vision and the appearance of perimacular and/or peripheral yellow-white flecks, with or without atrophy of the central retinal-pigment epithelium and a normal or only mildly abnormal flash electroretinogram when recorded in early stages of the disease."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: denaturing gradient gel electrophoresis, dHPLC, and SSCP analysis, PCR amplification of individual coding exons and flanking intron sequences, direct DNA sequencing

PreviouslyPublished: n/a

Variant: IVS13+1G→A; 2588G→C in trans "Correct segregation of disease alleles was demonstrated in all 39 cases in which family samples were available for study"

ClinVar: 7879

CAID: CA119128

SupplementalData: n/a

PMID: 30285522

Gene: ABCA4

Disease: Stargardt disease

unavailable publicly, accessed through UNC library

Case Annotation Template

Case#: Patient 40, female, Caucasian, onset at 2-3yo, Spain

DiseaseAssertion: STGD

FamilyInfo: Brother and Sister not affected showed heterozygous patterns of (p.His423Arg (c.1268A>G), IVS33+48 C>T) mutations. R1129L mutation heterozygous in the unaffected father; mutation not found in the unaffected mother. Patient has 4yo asymptomatic female child

CasePresentingHPOs: HP:0000505, HP: 0011463, HP:0030786, HP:0007641, HP:0007663, HP: 0000610, HP: 0007814, HP:0000007

CaseHPOFreeText: Macular yellow flecks, macular dystrophy

CaseNotHPOs: N/A

CaseNotHPOFreeText: Normal biomicroscopy

Genotyping Method: Conventional mutational screening on 77 STGD families and screened on the ABCR400 Microarray. Haplotype analyses, HR karyotypes, and MLPA were also performed.

PreviouslyPublished: N/A

Variant: p.Arg1129Leu (c.3386G>T)

CAID: CA227116

SupplementalData:N/A

PMID: 35413457

Gene: ABCA4

HGNC ID: 34

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

PMID: 32619608

Gene: ABCA4

Disease: Stargardt disease (STGD1)

ABCA4 localization in transgenic tadpoles showed retention of L541P in the IS (Fig. 2G and H). However, this assay does not meet the requirements for use of PS3 by the ClinGen ABCA4 VCEP.

PMID: 20149343

Gene: ABCA4

HGNC ID: 34

Case#: a 29-year-old man

DiseaseAssertion: Stargardt Disease

FamilyInfo: NR

CasePresentingHPOs: HP:0007663

CaseHPOFreeText: 20/70 visual acuity in both eyes

CaseNotHPOs: NR

CaseNotHPOFreeText: NR

Genotyping Method: ABCA4 microarray (ABCR5000 chip)

PreviouslyPublished: NR

Variant: NM_000350.3:c.5882G>A, p.G1961E and c.5018+2C>T (rare splice variant)

ClinVar: 7888, NR

CAID: CA119132, NR

SupplementalData: No CAID or ClinVar ID were found for the rare splice variant c.5018+2C>T

PMID: 10612508

Gene: ABCA4

HGNC ID: 34

Case#: Patient 4, Female, Caucasian, 33yo

DiseaseAssertion: STGD1

FamilyInfo: One of eight siblings; four affected. Disease segregates with ABCA4 variants consistent with autosomal recessive inheritance. Parents are deceased and can't be tested.

CasePresentingHPOs: HP:0007663, HP:0007754, HP:0025147, HP:0007924, HP:0011507

CaseHPOFreeText: gradual decline in visual acuity over 9 years, BCVA 20/300 OU, bilateral beaten-bronze appearance of the macula, numerous perimacular yellow flecks, fluorescein angiography showing hyperfluorescence in the posterior pole and dark choroid in the periphery

CaseNotHPOs: N/A

CaseNotHPOFreeText: absence of central hypofluorescence on fluorescein angiography (present in affected siblings but not this patient)

Genotyping Method: SSCP analysis; Taq Dyedeoxy Terminator Cycle Sequencing kit

PreviouslyPublished: N/A

Variant: NM_000350.3(ABCA4):c.2588G>C (p.Gly863Ala), NM_000350.3(ABCA4):c.161G>A (p.Cys54Tyr)

ClinVar: ClinVarID:7879, ClinVarID:99065

CAID: N/A

SupplementalData: Segregation and sequencing data (Figures 1, 4)

PMID: PMC7883928

Gene: ABCA4

HGNC ID: 34

Case#: Maia-Lopes Family 11 Proband 4613, Portuguese, 9yo at onset

DiseaseAssertion: STGD

FamilyInfo: Family 11

CasePresentingHPOs:

CaseHPOFreeText: severe central fundus changes, vision: FC/FC

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: ABCR400 microarray, dHPLC

PreviouslyPublished: n/a

Variant: c.[4926C>G(35)]+[5041_5055del(36)] / c.32T>C(1); p.(Ser1642Arg [10])+(Val1681_Cys1685del [10])/p.Leu11Pro

ClinVar: 99217

CAID: CA227106

SupplementalData: n/a

Case#: Male, 60

DiseaseAssertion: Stargardt disease

FamilyInfo: Possible macular degeneration in father

CasePresentingHPOs: HP:0007401, HP:0025010

CaseHPOFreeText: Vision was 20/40 in the right eye and 20/20 in the left eye. Dilated examination revealed scattered subretinal yellow flecks and macular atrophy bilaterally. The flecks were hyperautofluorescent. Fluorescein angiography showed obscuration of background choroidal fluorescence and window defects associated with the atrophy. Optical coherence tomography showed foveal atrophy and hyperreflective deposits at the level of the retinal pigment epithelium.

CaseNotHPOs: N/A

CaseNotHPOFreeText: Anterior segment examination was unremarkable. Normal cone and rod responses.

CasePreviousTesting: Target enrichment and next-generation sequencing were performed.

GenotypingMethod: N/A

PreviouslyPublished: N/A

Variant: Variant 1: NM_000350.3:c.5461-10T>C Variant 2: NM_000350.3:c.5603A>T

ClinVar: Variant 1: 92870 Variant 2: 99390

gnomAD: N/A

SupplementalData: Figure 1 shows fundus photographs (A and B), fundus autofluorescence (C and D), fluorescein angiography (E and F), near-infrared reflectance imaging (G), and an optical coherence tomography scan (H).

Case #: Male, 60 years old

DiseaseAssertion: He was diagnosed with late-onset Stargardts disease.

FamilyInfo: Has a family history with his father possibly having macular degeneration.

CasePresentingHPOs: HP:0007401, HP:0025010, HP:0012045 (sub-retinal/yellow), HP:0030602

CaseHPOFreeText: Proband presents with blurry vision (right eye) from over the past two years, with the right eye having 20/40 vision, while the left was 20/20. In addition to this, through dilation scattered subretinal yellow flecks and macular atrophy bilaterally, were revealed. The flecks were hyperautofluorescent. Obscuration of background choroidal fluorescence and window defects were also found. As well as foveal atrophy and hyperreflective deposits (RPE).

CaseNotHPOs: None found

CaseNotHPOFreeText: No abnormalities in the anterior segment examination. Through a full-field electroretinogram, normal rod and cone responses were found.

Genotyping Method: The genotyping was done through the use of target enrichment and next-generation sequencing.

PreviouslyPublished: N/a

Variant: 1) NM_000350.3(ABCA4):c.5461-10T>C 2) NM_000350.3(ABCA4):c.5603A>T (p.Asn1868Ile)

ClinVar: 1) 92870 2) 99390

CAID: N/a

gnomAD: 1) Highest minor allele frequency was 0.00031 (https://www.ncbi.nlm.nih.gov/clinvar/variation/92870/) 2) Highest minor allele frequency was 0.05787 (https://www.ncbi.nlm.nih.gov/clinvar/variation/99390/)

SupplementalData: I was able to find a variant (NM_000350.3(ABCA4):c.[5461-10T>C;5603A>T]) that addresses both of the variants. Also, Fig.1 shows the phenotype of the proband through tests.

PMID: 35243166

Gene: ABCA4

HGNC: 34

Case#: 93RE proband, Spanish

DiseaseAssertion: cone rod dystrophy

FamilyInfo: 1 affected sibling with the same genotype. het, carrier parents

CasePresentingHPOs: n/a

CaseHPOFreeText:

CaseNotHPOs: n/a

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: c.6410G>A (p.C2137Y); c.3988G>T (p.E1330X) found on WES. Cosegregation with GNAT2, ZNF513, OPA1, RP1L1

ClinVar: 2202779

CAID: CA341277358

SupplementalData: pedigree with genotype in supplemental file

PMID: 31130284

Gene: ABCA4

HGNCID: HGNC:34

SupplementalData: Table S4. Variant S2255I downgraded from Pathogenic to LB due to its high allele frequency.

Per ClinVar entry, this variant was associated with this paper. however, after reading through the genotypes, this variant was not found. Likely this paper was mentioned to support the statement that "Loss-of-function variants in ABCA4 are known to be pathogenic"

PMID: 24938718

Gene: ABCA4

Disease: retinitis pigmentosa

PMID: 30718709

Gene: ABCA4

Disease: retinal dystrophy

PMID: 22661472

Gene: ABCA4

Disease: Stargardt disease

Case#: a 46-year-old male

DiseaseAssertion: Pseudoxanthoma elasticum (PXE)

FamilyInfo: NR

CasePresentingHPOs: HP:0200034, HP:0011506, HP:0001102, HP:0025533, HP:0007401, HP:0200056, HP:0007754, HP:0031526, HP:0007663

CaseHPOFreeText: skin papules, CNV in right eye, angioid steaks, peau d'orange, peripheral comet lesions and macular atrophy at the poseterior pole (more severe in left eye). Juxtafoveal pigmented scar in right eye and fibrotic tissue at the interpapillomacular region in left eye. Pattern dystrophy-like changes were evident at posterior pole. OCT scan showed subretinal fluid with ellipsoid zone abnormalities at the fovea with juxtafoveal hyperreflective alteration corresponding to the fundus scar in the right eye. At the interpapillomacular region, the atrophy of the outer retinal layer and RPE was evident (hypertransmission phenomenon). In left eye, OCT scan showed widespread RPE atrophy with atrophy of the outer retinal layers. 6/10 visual acuity in right eye and 1/20 in left eye.

CaseNotHPOs: NR

CaseNotHPOFreeText: NR

Genotyping Method: Whole exome sequencing analysis focusing on 340 genes associated with the calcification process or inherited retinal diseases

PreviouslyPublished: NR

Variant: c.6647C>T, p.Ala2216Val, NM_000350.3

ClinVar: 236149

CAID: CA10602405

SupplementalData: NR

PMID: 32307445

Gene: ABCA4

Disease: Stargardt

This variant is listed for Stargardt DNAID#071103 in trans with c.1927G>A p.(Val643Met). No phenotype information provided.

This variant was transfected into HEK 293 cells and appears to show reduced expression and ATP-binding capacity, but no quantities were provided

L541P was purified, reconstituted into membranes, and tested for basal and retinal-stimulated ATPase activities. L541P was shown to have reduced basal ATPase, and no stimulation by retinal (Fig 4a)

PMID: 10396622

Gene: ABCA4

Disease: STGD, AMD

Case#: Hwang Case 3, female, 15yo at report, 7yo at onset

DiseaseAssertion: Stargardt

FamilyInfo: Family history was not significant for ocular disease.

CasePresentingHPOs: HP:0500087, HP:0011507

CaseHPOFreeText: difficulty reading materials held greater than 6 inches from her eyes, decreased visual acuity since age seven. BCVA was 20/150 OU. Posterior segment exam and autofluorescence was significant for bilateral central atrophy and pisciform fleck atrophy involving the peripapillary, macular, and peripheral regions OU (Figure 3, A and B).

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Genotyping was performed by the ABCR400 microarray followed by direct sequencing to confirm identified variants.

PreviouslyPublished: n/a

Variant: P1380L and R2030Q

ClinVar: 7904

CAID: CA129033

SupplementalData: n/a

Case#: 55 year old female

DiseaseAssertion: Stargardt

FamilyInfo: no significant ocular disease shown.

CasePresentingHPOs: difficulty reading materials 6 inches from her eyes, decreased visual acuity from age seven. BCVA was 20/150 OU. Posterior segment exam and autofluorescence was significant for bilateral central atrophy and pisciform fleck atrophy involving the peripapillary, macular, and peripheral regions.

CaseHPOFreeText: NR

CaseNotHPOs: NR

CaseNotHPOFreeText: NR

Genotyping Method: ABCR400 microarray

PreviouslyPublished: NR

Variant: NM_000350.3:c.4139C>T, NM_000350.3(ABCA4):c.6089G>A

ClinVar: 7904, 99428

CAID: CA129033

SupplementalData: NR

Case#: Hwang Case 2, female, 19yo at report, 18yo at onset

DiseaseAssertion: Stargardt

FamilyInfo: Family history was not significant for ocular disease

CasePresentingHPOs: HP:0007663, HP:0500087, HP:0011507

CaseHPOFreeText: difficulty reading, particularly in dim light; gradual difficulty in focusing. Visual acuity measured 20/40 OD and 20/150 OS. bilateral central atrophy, multiple fleck lesions, multiple clumps of yellowish deposits at the level of the retinal pigment epithelium in the posterior pole surrounded with some pigment clumping, and no evidence of atrophy of the retinal pigment epithelium. Autofluorescence imaging revealed multifocal atrophic lesions involving the central macula and peripheral hyperautofluorescent flecks OU. The peripapillary regions demonstrated atrophic flecks OU without confluent atrophy (Figure 2, A and B).

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Genotyping was performed by the ABCR400 microarray followed by direct sequencing to confirm identified variants.

PreviouslyPublished: n/a

Variant: P1380L homozygous

ClinVar: 7904

CAID: CA129033

SupplementalData: n/a

previously reported in PMID: 26377081

Case#: Patient 8, 13yo at report, British Columbia, Canada

DiseaseAssertion: Stargardt disease

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: stage 4 Fishman classification (extensive choroid and RPE atrophy throughout the fundus, decreased ERG cone and rod amplitudes, and moderate to severe peripheral field restriction). Visual acuity= 20/200

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: exons and exon-intron boundaries of ABCA4, CNGB3, and ELOVL4 were sequenced

PreviouslyPublished: n/a

Variant: L541P; A1038V phase unknown, but likely a complex allele

ClinVar:

CAID: CA226911

SupplementalData: n/a

In HEK293T cells, p.Val552Ile expresses at close to WT levels, exhibits normal N-Ret-PE binding properties, and has only a modest reduction in ATPase activity. Consistent with mild disease phenotype

As shown in other publications, the ATPase activity of this variant appears to be drastically reduced compared to WT when transfected into HEK293 cells, but expression is comparable to WT.

PMID: 33090715

Gene: ABCA4

Disease: retinal dystrophy

This paper is listed in LOVD as containing this variant. Unable to find the variant in the main text and unable to locate the supplemental info. At the end of the paper, it says supplemental info can be found online, so used the DOI linked at the end of the article but it just leads to a PDF again with no supplemental

PMID: 31980526

Gene: ABCA4

Disease: adults ≥18 y old without acute illness, activity-limiting unexplained illness or symptoms, or known active cancer

prospective cohort study: 3-y precision medicine study with a goal to integrate whole-genome sequencing with deep phenotyping.

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 #16, male, 6yo at onset, Brazilian

DiseaseAssertion: stargardt

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: type II (an area of foveal hypofluorescence surrounded by an area with a heterogeneous appearance and hyperautofluorescent and hypoautofluorescent points that extend to the temporal arcades, giving the retina a reticulate appearance). visual acuity: OD=20/150, OS=20/200

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: c.4720G>T p.(Glu1574*), no second variant. NGS and conclusive molecular testing regarding other Stargardt genes were excluded

ClinVar: 1460063

CAID: CA341283936

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#010477, Chinese, male, 18yo at onset

DiseaseAssertion: stargardt

FamilyInfo: n/a

CasePresentingHPOs: STGD1 diagnosis based on the following criteria: "a bilateral central vision defect; fundus displaying a beaten-bronze appearance and/or orange-yellow flecks in the retina from the macula to the midperiphery; fluorescein angiography presenting with a typical dark choroid; and normal to subnormal ERG results." BCVA=0.4/ 0.5

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: p.P2097S; c.2255G>T p.(Ser752Ile) phase unknown

ClinVar: 2202780;

CAID: CA341277622;

SupplementalData: supplementary table S4 has phenotype information

Case#: Patient#010382, Chinese, male, 29yo at onset

DiseaseAssertion: stargardt

FamilyInfo: n/a

CasePresentingHPOs: STGD1 diagnosis based on the following criteria: "a bilateral central vision defect; fundus displaying a beaten-bronze appearance and/or orange-yellow flecks in the retina from the macula to the midperiphery; fluorescein angiography presenting with a typical dark choroid; and normal to subnormal ERG results." BCVA=0.4/ 0.6

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: p.P2097S; c.6050G>A p.(Cys2017Tyr) phase unknown

ClinVar: 2202780;

CAID: CA341277622;

SupplementalData: supplementary table S4 has phenotype information

This variant is in Figure 2 as an ABCA4 disease-associated allele identified in Spanish Stargardt disease (STGD) patients with a frequency below 5%. No additional information about phenotype or genotype is provided and a future paper focusing on those details, by the same first author (PMID: 23755871), so they are likely the same patient in the same cohort

Case#: a 56-year-old female

DiseaseAssertion: Pseudoxanthoma elasticum (PXE)

FamilyInfo: NR

CasePresentingHPOs: HP:0200034, HP:0001102, HP:0025533, HP:0011506, HP:0500087

CaseHPOFreeText: Papules on neck and axillae, marked skin laxity and redundance in neck, axillae, periumbilican area, groyne, and inner thighs, angioid streaks, peau d'orange. In right eye, a CNV, a large peripapillary atrophy, a small iuxafoveal scar, and RPE-Bruch's membrane complex normalities nasally to the fovea.

CaseNotHPOs: NR

CaseNotHPOFreeText: NR

Genotyping Method: Next generation sequencing focusing on 362 genes associated with calcification-related diseases and inherited retinal diseases

PreviouslyPublished: NR

Variant: c.1928T>G, p.Val643Gly, NM_000350.3

ClinVar: 99102

CAID: CA226958

SupplementalData: This variant has been reported likely pathogenic in VarSome and literature.

This variant is found without ala1038val in patient 5. Patient 5 is a 36yo white female. Visual acuity= OD:10/120, OS:10/60-1. Central scotome. Type 1 fundus=diffuse pigmentary degenerative changes. Cone responses more reduced than rod amplitudes on ERG. Second variant: Asp600Tyr. Phase not confirmed

PMID: 25346251

Gene: ABCA4

Disease: Stargardt

PMID: 18334942

Gene: ABCA4

HGNC ID: 34

Case#: patient 33, male, Spanish

DiseaseAssertion: STGD

FamilyInfo: Figure 1. Both parents and two siblings of the proband were heterozygous for ABCA4 c.5413A>G allele. Sister affected despite heterozygosity.

CasePresentingHPOs: HP:0007663, HP:0030786, HP:0007722

CaseHPOFreeText: myopia, astigmatism, opafication of posterior pole of lens, hyperpigmentation, a few central yellowish flecks, shallow peripheral scotomas in both eyes, full-field ERG response showed slightly reduced—but still within the normal range—amplitudes for rod, mixed cone-rod, cone single flash, and cone flicker, respectively.

CasePreviousTesting: n/a

GenotypingMethod: microarray

PreviouslyPublished: 11385708, 12442277

Variant: ABCA4 p.Asn1805Asp (c.5413A>G)

ClinVar: 99373 https://www.ncbi.nlm.nih.gov/clinvar/variation/99373/?term=%22ABCA4%22%5BGENE%5D+AND+%22p.Asn1805Asp%22%5BVARNAME%5D+AND+%22(c.5413A%3EG)%22%5BVARNAME%5D

gnomAD: 0.000009292 https://gnomad.broadinstitute.org/variant/1-94014590-T-C?dataset=gnomad_r4

PMID: 18334942

Gene: ABCA4

HGNCID: 34

Case#: patient 26, female, Spanish

DiseaseAssertion: early onset RP

FamilyInfo: Figure 1. One brother homozygous for ABCA4 c.5413A.G allele, parents and one brother heterozygous for ABCA4 c.5413A>G allele. All three brothers and father carriers of p.Cys948Tyr allele on the CRB1 gene. Mother heterozygous for p. Trp822ter (c.2465G>A)

CasePresentingHPOs: HP:0000662, HP:0001133, HP:0007663,

CaseHPOFreeText: hyperopia, astigmatism, nystagmus, roundish pigments distributed across entire retina including peripheral retina, posterior pole, and macular region, filiform constriction on retinal vessels.

CasePreviousTesting: N/A

GenotypingMethod: Microarray

PreviouslyPublished: 11385708, 12442277

Variant: ABCA4 p.Asn1805Asp (c.5413A>G)

ClinVar: 99373 https://www.ncbi.nlm.nih.gov/clinvar/variation/99373/?term=%22ABCA4%22%5BGENE%5D+AND+%22p.Asn1805Asp%22%5BVARNAME%5D+AND+%22(c.5413A%3EG)%22%5BVARNAME%5D

gnomAD: 0.000009292 https://gnomad.broadinstitute.org/variant/1-94014590-T-C?dataset=gnomad_r4

PMID: 31522899

Gene: ABCA4

Disease: Stargardt

Case#: Family 16, P37, female, Netherlands 13yo at onset

DiseaseAssertion: Stargardt

FamilyInfo: 1 affected sibling with same genotype

CasePresentingHPOs:

CaseHPOFreeText: visual acuity: OD=0.22, FAF images consistent with STGD1

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Sanger

PreviouslyPublished: n/a

Variant: c.5196+1137G>A; c.859-506G>C

ClinVar: 438100

CAID: CA26843511

SupplementalData:

Case#: Patient 721, male, 41yo at entry

DiseaseAssertion: Stargardt disease

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: category IIA (autosomal recessive stargardt disease)

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: one or more of the following approaches: automated Sanger sequencing with an ABI 3730xl sequencer, allele-specific genotyping with a Fluidigm EP1, amplification refractory mutation system (ARMS 17), chromosomal microarray analysis, and/or plasmid cloning of PCR products followed by Sanger sequencing. WES, WGS

PreviouslyPublished: n/a

Variant: c.6416G>C p.Arg2139Pro; c.2588G>C p.Gly863Ala. confirmed in trans

CAID: CA10611614

SupplementalData: supplemental table 1

PMID: 19352439

Gene: ABCA4

PMID:39967245

Gene: ABCA4

HGNC ID: 34

Case#:39-year-old man

DiseaseAssertion:

FamilyInfo:

CasePresentingHPOs:omplained of visual impairment with night blindness

CaseHPOFreeText:NA

CaseNotHPOs:NA

CaseNotHPOFreeText:NA

Genotyping Method:SAnger Seqencing

PreviouslyPublished:

Variant:WDR19 variants: the novel deletion at c.1777 + 1 within the donor splicing site (class 4) and the rare c.1430 G>T variant causing the amino-acid substitution p.(Arg477Leu) (class 3) in the putative protein. Additionally, a heterozygous c.1793A>G (class 3) variant in the CDH23 gene was found, though it was deemed as not contributive to the patient’s clinical phenotype. All reported variants were confirmed through Sanger sequencing.

ClinVar:NA

CAID:Na

SupplementalData:NA

This variant is reported in Table S6, but only location, predictions, frequencies, etc are reported for it, not cases.

This variant is reported in Table S6, but only location, predictions, frequencies, etc are reported for it, not cases.

PMID: 32884132

Gene: ABCA4

Disease: Stargardt

Article is a PDF, so annotating here. In the supplemental file (table S1), this variant was listed as being included on the microarray, but that is all the information provided.

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

This variant was found on one allele of a Stargardt patient, but no additional details are provided about the patient or the other allele. A combination of single-strand conformation polymorphism (SSCP) and automated DNA sequencing was used to evaluate the entire exonic and flanking intron sequence of the ABCA4 gene

Case#: Eisenberger Patient 92, female, 31yo, German

DiseaseAssertion: Autosomal dominant RP

FamilyInfo: non-consanguineous

CasePresentingHPOs:

CaseHPOFreeText: "The diagnoses of all patients were established by medical history, family history and detailed clinical evaluation of vision. Ophthalmological examination included stereoscopic funduscopy, standard ERG, perimetry, measurement of dark adaptation, and determination of best-corrected visual acuity in most patients."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: NGS for the exons of 55 RP and LCA genes, Sanger for confirmation

PreviouslyPublished: n/a

Variant: Allele 1: RHO c.180C>A p.Tyr60; Allele 2*: ROM1: c.178C>A p.Pro60Thr; c.323C>T p.Thr108Met;

ABCA4: c.1654G>A p.Val552Ile; c.5714+5G>A; <br /> RP2: c.844C>T p.Arg282Trp; <br /> RPGRIP1: c.2510C>G p.Ala837Gly

ClinVar:

CAID: CA239745

SupplementalData: n/a

Annotating here since unable on the PDF.

Case 3 is a 6yo male. VA: OD: 20/150, OS: 20/200. Proband had macular atrophy and flecks at the posterior pole. In the autofluorescence exam, there was peripapillary sparing of the hyper-autofluorescent flecks. On OCT images the atrophic areas at the macula correlated to disruption of the elipsoid layer and decrease in the foveal thickness. OCT showed loss of the photoreceptor layer and EPR layer. Proband has only 1 ABCA4 variant, so not eligible for PP4. Also has a variant in PROM1 (p.Ala643Gly). ABCA4, PROM1, and ELOVL4 genes sequenced by next-generation sequencing (NGS) test.

Case#: German/British, 76

DiseaseAssertion: EOSRD

FamilyInfo: Grandparents from Germany and the United Kingdom

CasePresentingHPOs: HP:0007401, HP:0007913

CaseHPOFreeText: Macular atrophy and pigmentation, peripheral pigmentation, early-onset severe retinal dystrophy

CaseNotHPOs: N/a

CaseNotHPOFreeText: N/a

Genotyping Method: BGISeq-500 2 x 100-bp paired-end module, Burrows-Wheeler Aligner and Genome Analysis Tooklit HaploptypeCaller

PreviouslyPublished: n/a

Variant: c.1622T>C, c.4326C>A, and c.3113C>T

ClinVar: 99067, 417991, 7894

CAID: CA226911, CA957653, CA119135

SupplementalData: The c.1622T>C variants and c.3133C>T are thought to be same gene copy

PMID: 39421326 (PMCID: PMC11675205)

Gene: ABCA4

HGNC ID: 34

Case#: Patient 24 (male)

DiseaseAssertion: STGD (Stargardt disease)

FamilyInfo: Caucasian family from Germany. Patient has two siblings carrying the variant but they are not clinically affected according to pedigree information.

CasePresentingHPOs: Decreased central visual acuity (HP:0000545) Macular atrophy (HP:0007754) Retinal flecks (HP:0030638) Abnormal fundus autofluorescence (HP:0030647) Macular degeneration (HP:0007754) Abnormal electroretinogram (HP:0000763)

CaseHPOFreeText: Male patient diagnosed before age 50 with Stargardt disease. Best corrected visual acuity (BCVA) approximately 0.05–0.2. Fundus imaging shows paracentral scotoma, macular atrophy, and hyperfluorescent flecks with sparing of the fovea. Autofluorescence demonstrates hyperreflective spots and patchy lesions with parafoveal involvement.

CaseNotHPOs: None explicitly reported.

CaseNotHPOFreeText: Pattern-like distribution of lesions noted on clinical examination.

Genotyping Method: Whole-exome sequencing (WES) with an in-house RD-associated gene panel including 619 candidate and disease-associated genes.

PreviouslyPublished: No (novel complex deep-intronic allele described in this study).

Variant: c.[1555-5882C>A;1555-5784C>G]

ClinVar: Not reported in ClinVar in the provided information.

CAID: CA272741; CA227172

SupplementalData: Segregation data and functional splicing analysis available in the supplemental data (Table S1, Figure S1) of the article.

Case#: Bertelsen Patient D023, female, 9yo at onset

DiseaseAssertion: generalized choriocapillaris dystrophy

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: end-stage generalized choriocapillaris dystrophy characterized by semiconfluent multifocal areolar outer retinal atrophy, the severity of which decreases with increasing eccentricity. Central patches of visible sclera are surrounded by coarse confluent hyperpigmentation. The periphery shows isolated or clustered hyperpigmentation. In and around the fovea there is pronounced atrophy of the retinal pigment epithelium, the photoreceptor layer, and the outer nuclear layer and intraretinal hyperreflective material corresponding to the hyperpigmentation

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: microarray

PreviouslyPublished: n/a

Variant: c.203C>T p.P68L; c.3329-2A>G

ClinVar: 99113

CAID: CA226972

SupplementalData: n/a

Case#: Patient #43, male, 9yo at onset, 16yo at report, German

DiseaseAssertion: macular dystrophy or cone-rod dystrophy

FamilyInfo: inheritance= sporadic. phase not confirmed, but no other affected family members and no parental consanguinity

CasePresentingHPOs:

CaseHPOFreeText: reduced visual acuity, erg scotopic= reduced, erg-photopic=reduced

CaseNotHPOs:

CaseNotHPOFreeText: syndromic retinal disease, age-related macular degeneration, central serous retinopathy, autoimmune retinopathy, retinal vascular disease, achromatopsia, X-linked retinoschisis, North Carolina macular dystrophy

CasePreviousTesting: n/a

GenotypingMethod: Sanger sequencing of ABCA4

PreviouslyPublished: n/a

Variant: c.3098del (p.Lys1033Serfs*51); c.3243G>T (p.Lys1081Asn)

ClinVar: 236516

CAID: CA10581650

SupplementalData: Supplementary table 1

Case#: Patient 231, Female, age of onset at 7 y.o, Poland

DiseaseAssertion: STGD1

FamilyInfo: Mother was a carrier, unaffected father.

CasePresentingHPOs: HP:0007722, HP:0000608, HP:0025158

CaseHPOFreeText: RPE atrophy, macular degeneration, central hyper-autofluorescence in fundus autofluorescence

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a, non-proband identified HPO's mentioned, but not assignable to individual proband.

Genotyping Method: DNA isolated from peripheral blood from patients and relatives via MagNA Pure 24, samples screened with MIPs targeting 108 genes involved in pathogensis of IRD's. PCR completed on library, analysed with NGS fragment analysis kit.

PreviouslyPublished: yes

Variant: c.5882G>A

ClinVar:7888

gnomeAD: 0.00310 allelic freq.

CAID: n/a

SupplementalData: Fig1: List of families displaying pseudo-dominant inheritance. Fig2: Number of alleles for most common variants.

This paper is evaluating potential hotspots of ABC genes. The variant is mentioned as being in the C-loop2 motif, but no further information is provided on the variant.

This variant is found in compound heterozygosity with c.3386G>T p.(Arg1129Leu) in family MD-0560 in a previous publication (PMID: 23755871)

MonDO: MOND:08000406

Case: Female, onset 6 years VA 20/200 OU identify 1 ouf 15 Ishiara cards and overlooking symptom. Presumably diagnosed with Batten disease but found to harbor genetic variant for Stargardt disease.

DiseaseAssertion: Stargardt disease

FamilyInfo: No family history of visual loss in childhood.

"CasePresentingHPOs: HP:0007663, HP:0007988, HP:0030584, HP:0008043, HP:0008001, HP:0030609 (Reduced visual acuity, Macular hypopigmentation, Color vision test abnormality, Retinal arteriolar constriction, Foveal hyperpigmentation, Photoreceptor layer loss on macular OCT"

CaseHPOFreeText: bull's eye lesions, prominent overlooking, hyperreflective granular deposits

CaseNOTHPOFreeText: HP:0001336, HP:0001250, HP:0000648, HP:0000707

CasePreviousTesting: (Myoclonus, Seizure, Optic atrophy, Abnormality of the nervous system

GenotypingMethod: Genetic testing was negative for all mutations known to cause neuronal ceroid lipofuscinosis, but whole exome sequencing showed compound heterozygosity for 2 pathogenic variants in the ABCA4 gene

MultipleGeneVariants:

(1) GeneName: ABCA4

(1) Variant: c.3007C>T, p.Q1003X

(1) ClinVarID or CAID: CA119132

(1) gnomAD: 0.003406 total AF in gnomAD v4.1 (https://gnomad.broadinstitute.org/variant/1-94008251-C-T?dataset=gnomad_r4)

(2) GeneName: ABCA4

(2) Variant: c.768G>T

(2) ClinVarID or CAID: CA227458

(2) gnomAD: 0.00007930 total AF in gnomAD v4.1 (https://gnomad.broadinstitute.org/variant/1-94098794-C-A?dataset=gnomad_r4)

PMID: 35112029

Gene: ABCA4

HGNC ID: 34

This variant is found in Table S5. "Five probands with one ABCA4 disease-associated allele" Proband #89. Since this proband has only one variant they are not eligible for PP4

Case#: Patient STG-16, 13yo at onset, Argentina

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: BCVA=0.7/0.7, FA=3B, AF pattern=2, OCT showed decreased retinal thickness with disruption of external layers

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: NGS of ABCA4 (NM_000350.2), ELOVL4 (NM_022726.3), PROM1 (NM_006017.2), and CNGB3 (NM_019098.4)

PreviouslyPublished: n/a

Variant: c.4457C>T (p.Pro1486Leu); c.1804C>T (p.Arg602Trp)

ClinVar: 99283

CAID: CA227192

SupplementalData: supplementary table 2 has genotype/phenotype info

PMID: 33841504

Gene: ABCA4

Disease: Stargardt

PMID: 32653833

Gene: ABCA4

Disease: Stargardt

Case#: Patient #15, Moorfields Eye Hospital, London, UK, female, 39yo at onset, 51yo at report,

DiseaseAssertion: ABCA4-Associated Retinopathy, clinical diagnosis of STG

FamilyInfo: no additional family-member WGS data available

CasePresentingHPOs:

CaseHPOFreeText: BCVA= OD: 6/9, OS: 6/9, Fishmann Classification=2 (fleck-like lesions anterior to the vascular arcades and/or nasal to the optic disc), early changes to foveal photoreceptors, Extent of FAF abnormalities with Regard to Vascular Arcades: beyond. ffERG Group: 1(normal). PERG: Abnormal. FAF in Fig. 1B. characteristic yellow-white pisciform flecks in the RPE of the posterior pole that were hyperautofluorescent on FAF imaging or progressive atrophy of the macular RPE

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Haplotype analysis, ABCA4 mutation screening was performed by next-generation sequencing, sequenced as part of the retinal panel at the Molecular Vision Lab

PreviouslyPublished:

Variant: c.5196+1137G>A p.[=,M1733Efs∗78] c.[1715G>A;2588G>C] p.[(R572Q;G863A,G863del]

ClinVar: 7900

CAID: CA226918

SupplementalData:

Case#: Proband 95-0103, Spanish, onset at 8yo

DiseaseAssertion: cone-rod dystrophy

FamilyInfo: Family RP-0298. Affected sister, 95-0101, with same genotype

CasePresentingHPOs: HP:0001133, HP:0000529, HP:0000662, HP:0000512, HP:0000543, HP:0007737, HP:0007641, HP:0007787

CaseHPOFreeText: BCVA=0.1/0.1; ERG: scotopic-Low amplitude, normal latency, photopic-abolished, mixed-diminished a and b waves; dense pigment accumulation at macular region;, bilateral posterior subcapsular cataract.

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: 19365591

Variant: c.4720G>T p.E1574; c.950delG p.G317Afs57. WES, All patients were previously tested and all resulted to be negative for known autosomal recessive retinitis pigmentosa (ARRP) or Leber Congenital Amaurosis (LCA) mutations by microarray screening

ClinVar: 1460063

CAID: 341283936

SupplementalData: Table S2 has phenotype details

PMID: 23940504

Gene: ABCA4

Disease: retinal dystrophy