PMID: 24713488

Gene: ABCA4

Disease: ABCA4-Associated Retinopathies

This variant is included in a table that lists all ABCA4 variants

This variant is listed for Stargardt DNAID#070949 in trans with c.3682G>A p.(Glu1228Lys). No phenotype information provided.

Case#: Male, Family#3, Proband M1, M2: II,1 on pedigree

DiseaseAssertion: STGD

FamilyInfo: mother of proband has p.N18681 and p.P1380L mutations and is asymptomatic with no changes to NIR-AF and SD-OCT. Treated with 400mg of hydroxychloroquine for lupus prior to imaging. Non-affected father.

CasePresentingHPOs:HP:0007663, HP:0000493

CaseHPOFreeText: Proband has reduced visual acuity and issues reading with BCVA 20/200 in R.E and 20/50-2 in L.E. Oval foveal lesions with stage 2 flecks. Visual acuity reducing starting at age 10.

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: Genotyping performed at Columbia University, sequencing technology used is not disclosed.

PreviouslyPublished: n/a

Variant: M1:p.P1380L, complex allele: M2: p.N18681 and IVS38:c.5461-10T>C. M3: c.4139C>T(p.P1380L)

ClinVar: M1) 99390 M2) 99067 M3) Variation ID: 7904

CAID: n/a

SupplementalData: Fig 1: Pedigree illustrating ABCA4 variants and the associated Stargardt phenotype for 5 families. Proband Labeled w/ white arrow for each family. Fig 2: retinal scan measuring melanin in 4 patients of family 2. Panel shows bull's-eye ring of RPE atropy. Fig 3: Macular SD-OCT line profile from b-scans. Reflectivity plotted against function of retinal depth. Table 1: table shows patients with p.N18681 variant, type of mutation, and pathogenicity class. Table 2: Patients, age on-set and first symptom

PMID: PMC6548695

Gene: ABCA4

HGNC ID: 34

Case#: Case1, Sex:Female, Age:35

DiseaseAssertion: STGD

FamilyInfo: n/a

CasePresentingHPOs: n/a

CaseHPOFreeText: Clinical Notes: the patient reported an ocular trauma in the right eye, which required hospitalization and caused sudden loss of vision at the age of 9 years. In 1998, at our first observation, visual acuity was 20/1,000 in the right eye and 20/600 in the left eye.

CaseNotHPOs:n/a

CaseNotHPOFreeText: n/a

Genotyping Method: genetic analysis

PreviouslyPublished: n/a

Variant: Variant is a heterozygous mutation given as (N965S/G1961E); NM_000350.3(ABCA4):c.2894A>G (p.Asn965Ser) /NM_000350.3(ABCA4):c.5882G>A (p.Gly1961Glu)

ClinVar: Variation ID: 236096 / Variation ID: 7888

SupplementalData: n/a

Case#: Case 3, Sex: Male, Age:21

DiseaseAssertion: STGD

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: Text mentions BCVA of 20/200 in both eyes. Pigmentary changes in macula associated with flecks, small inferior juxta-papillar area of subretinal fibrosis in right eye, left eye legion localized in posterior pole macula temporally. Instable fixation in right eye. Low retinal mean sensitivity in both eyes.

CaseNotHPOs:n/a

CaseNotHPOFreeText: Healthy ocular adnexa and specular transparent and 'in situ' lens. Visual acuity stable. Stable fixation in left eye.

Genotyping Method: genetic analysis

PreviouslyPublished: n/a

Variant: Variant is a heterozygous mutation given as NM_000350.3(ABCA4):c.3212C>T (p.Ser1071Leu) / NM_000350.3(ABCA4):c.667A>C (p.Lys223Gln) / NM_000350.3(ABCA4):c.3607G>A (p.Gly1203Arg)

ClinVar: Variation ID: 99208 / Variation ID: 845426/ Variation ID: 417989

SupplementalData: n/a

PMID: 28050124

Gene: ABCA4

HGNC ID: 34

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#: Cideciyan Case #86, male, 20.5yo at report

DiseaseAssertion: "clinical diagnosis within the spectrum of Stargardt disease or cone–rod dystrophy caused by ABCA4 mutations."

FamilyInfo: Parental segregation of the reported alleles confirmed. P87 is the proband's sibling, affected, same genotype

CasePresentingHPOs:

CaseHPOFreeText: LDF eccentricity along principal meridians [deg]: superior=16.9, inferior=11.7, temporal=18.9, inner nasal=9.6, outer nasal=18.9

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: NGS

PreviouslyPublished: PMID: 24550365

Variant: c.203 C>T p.Pro68Leuc.5882 G>A p.(Gly1961Glu); c.5882 G>A p.(Gly1961Glu). Phase confirmed.

ClinVar: 99113

CAID: CA226972

SupplementalData: table s1

PMID:35973334

Gene: ABCA4

HGNC ID: 34

Case#: eldest sister II.2 aged 22 year

Variant splice-site variant NC_000003.11(NM_016247.3):c.1239 + 1G > T [Chr3:100972539C > A

FammilyInfo two-generation north Indian family with three members affected with Stargardt-like macular dys trophy

CasePresentingHPOs:ow vision and difficulty in night vision, with symptoms starting in the early second decade of life, which progressed slowly over time

PedrigreeIn the results section is mentioned

CaseHPOFreeText:NA

CaseNotHPOs:Na

CaseNotHPOFreeText:NA

Genotyping Method:2.3. Validation of identified variant by Sanger sequencing

PreviouslyPublished:NA

PMID: 40948369

Gene: ABCA4

HGNC ID: 34

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:

PMID: 35112029

Gene: ABCA4

HGNCID: HGNC:34

Case#: Family MD-0247/ARDM-247 Proband, 12yo at onset

DiseaseAssertion: AR cone rod dystrophy

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=0.05/0.1, cone-pattern on ERG

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: c.6410G>A (p.Cys2137Tyr); c.3386G>T (p.Arg1129Leu) found by ABCR400 + dHPLC + HRM

ClinVar: 2202779

CAID: CA341277358

SupplementalData: n/a

PMID: 18024811

Gene: ABCA4

Disease: bull's-eye maculopathy

Case#: Maia-Lopes Family 18 Proband 5709, Portuguese, 9yo at onset

DiseaseAssertion: STGD

FamilyInfo: Family 18

CasePresentingHPOs:

CaseHPOFreeText: mild central fundus changes, vision: 2/10 / 2/10

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: ABCR400 microarray, dHPLC

PreviouslyPublished: n/a

Variant: c.1804C<T/ c.32T>C(1); p.Arg602Thr/p.Leu11Pro

ClinVar: 99217

CAID: CA227106

SupplementalData: n/a

In supplemental table S2, Case LL291 is a female listed as "likely solved" with a clinical diagnosis of CRD. Proband is compound heterozygous for c.32T>C p.(Leu11Pro) and c.5196+1137G>A.

In Supplemental table S1, this proband is a female, 54yo at report, 50yo at onset. Nyctalopia, visual acuity=0.05/0.6, OD: extremely high myopia OS: high myopia, no family information

Supplementary table 2 lists this variant as previously reported in 3 individuals from PMID: 19365591

Eight families that are not labelled all have this variant and pedigrees to show family information in supplemental figure s2.

Case#: Braun Family 5 Proband (from left to right, top to bottom of available pedigrees), male

DiseaseAssertion: Stargardt

FamilyInfo: Proband has 1 affected sister with the same genotype and 1 unaffected, heterozygous brother. Genotypes not provided for parents.

CasePresentingHPOs:

CaseHPOFreeText: "five or more of the following features of ABCA4-associated retinal disease: decreased visual acuity before age 20, decreased visual acuity as the first visual symptom, symmetrical fundus findings, pisciform flecks, beaten metal macular atrophy, bulls-eye maculopathy, peripapillary sparing, vermillion fundus, masked choroid on fluorescein angiography, nummular pigment overlying extensive macular atrophy, central outer retinal atrophy on optical coherence tomography and central scotomas on Goldmann perimetry."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: one plausible disease-causing mutation detected in ABCA4 after assessing the entire coding sequence and canonical retinal splice junctions with automated bidirectional Sanger sequencing using an ABI 3730 sequencer

PreviouslyPublished: n/a

Variant: c.5196+1137G>A; c.4363T>C (p.C1455R)

ClinVar: 438100

CAID: CA26843511

SupplementalData: pedigree in fig s2

Case#: Braun Family 1 Proband (from left to right, top to bottom of available pedigrees), female

DiseaseAssertion: Stargardt

FamilyInfo: Both parents are unaffected heterozygotes. c.4139C>T (p.P1380L) paternally inherited, c.5196+1137G>A maternally inherited. Proband has 2 unaffected, heterozygous children.

CasePresentingHPOs:

CaseHPOFreeText: "five or more of the following features of ABCA4-associated retinal disease: decreased visual acuity before age 20, decreased visual acuity as the first visual symptom, symmetrical fundus findings, pisciform flecks, beaten metal macular atrophy, bulls-eye maculopathy, peripapillary sparing, vermillion fundus, masked choroid on fluorescein angiography, nummular pigment overlying extensive macular atrophy, central outer retinal atrophy on optical coherence tomography and central scotomas on Goldmann perimetry."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: one plausible disease-causing mutation detected in ABCA4 after assessing the entire coding sequence and canonical retinal splice junctions with automated bidirectional Sanger sequencing using an ABI 3730 sequencer

PreviouslyPublished: n/a

Variant: c.5196+1137G>A; c.4139C>T (p.P1380L)

ClinVar: 438100

CAID: CA26843511

SupplementalData: pedigree in fig s2

Case#: Braun Family 7 Proband (from left to right, top to bottom of available pedigrees), female

DiseaseAssertion: Stargardt

FamilyInfo: Unaffected carrier parents. c.5196+1137G>A maternally inherited; c.4561-10T>C paternally inherited

CasePresentingHPOs:

CaseHPOFreeText: "five or more of the following features of ABCA4-associated retinal disease: decreased visual acuity before age 20, decreased visual acuity as the first visual symptom, symmetrical fundus findings, pisciform flecks, beaten metal macular atrophy, bulls-eye maculopathy, peripapillary sparing, vermillion fundus, masked choroid on fluorescein angiography, nummular pigment overlying extensive macular atrophy, central outer retinal atrophy on optical coherence tomography and central scotomas on Goldmann perimetry."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: one plausible disease-causing mutation detected in ABCA4 after assessing the entire coding sequence and canonical retinal splice junctions with automated bidirectional Sanger sequencing using an ABI 3730 sequencer

PreviouslyPublished: n/a

Variant: c.5196+1137G>A; c.4561-10T>C

ClinVar: 438100

CAID: CA26843511

SupplementalData: pedigree in fig s2

Case#: Braun Family 2 Proband (from left to right, top to bottom of available pedigrees), female

DiseaseAssertion: Stargardt

FamilyInfo: Both parents are unaffected carriers. c.1622T>C (p.L541P) and c.3113C>T (p.A1038V) complex variants were paternally inherited, c.5196+1137G>A maternally inherited.

CasePresentingHPOs:

CaseHPOFreeText: "five or more of the following features of ABCA4-associated retinal disease: decreased visual acuity before age 20, decreased visual acuity as the first visual symptom, symmetrical fundus findings, pisciform flecks, beaten metal macular atrophy, bulls-eye maculopathy, peripapillary sparing, vermillion fundus, masked choroid on fluorescein angiography, nummular pigment overlying extensive macular atrophy, central outer retinal atrophy on optical coherence tomography and central scotomas on Goldmann perimetry."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: one plausible disease-causing mutation detected in ABCA4 after assessing the entire coding sequence and canonical retinal splice junctions with automated bidirectional Sanger sequencing using an ABI 3730 sequencer

PreviouslyPublished: n/a

Variant: c.5196+1137G>A; c.1622T>C (p.L541P) and c.3113C>T (p.A1038V) complex variant

ClinVar: 438100

CAID: CA26843511

SupplementalData: pedigree in fig s2

Case#: Braun Family 3 Proband (from left to right, top to bottom of available pedigrees), female

DiseaseAssertion: Stargardt

FamilyInfo: Both parents are unaffected, but only mother has genotype information available since father is deceased. c.1622T>C (p.L541P) and c.3113C>T (p.A1038V) complex variants were maternally inherited.

CasePresentingHPOs:

CaseHPOFreeText: "five or more of the following features of ABCA4-associated retinal disease: decreased visual acuity before age 20, decreased visual acuity as the first visual symptom, symmetrical fundus findings, pisciform flecks, beaten metal macular atrophy, bulls-eye maculopathy, peripapillary sparing, vermillion fundus, masked choroid on fluorescein angiography, nummular pigment overlying extensive macular atrophy, central outer retinal atrophy on optical coherence tomography and central scotomas on Goldmann perimetry."

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: one plausible disease-causing mutation detected in ABCA4 after assessing the entire coding sequence and canonical retinal splice junctions with automated bidirectional Sanger sequencing using an ABI 3730 sequencer

PreviouslyPublished: n/a

Variant: c.5196+1137G>A; c.1622T>C (p.L541P) and c.3113C>T (p.A1038V) complex variant

ClinVar: 438100

CAID: CA26843511

SupplementalData: pedigree in fig s2

This variant is found in table S2A to have an OR of infinity with a CI (10.92-infinity).

This variant is found in table S2A to have an OR of infinity with a CI (25.35-infinity), so PS4 is applicable

This variant is found in table S2A to have an OR of infinity with a CI (14.02-infinity), so PS4 is applicable

This variant was not evaluated.

This variant was not evaluated.

This variant is found in table S2A to have an OR of 47.7 with a CI (4.71-2311.43).

PMID: 33261146

Gene: ABCA4

Disease: ABCA4-Associated Retinal Dystrophies

Case#: Somali origin, 11 years of age, onset age 8

DiseaseAssertion: STGD

FamilyInfo: Parents were heterozygous for Arg212Cys, asymptoamtic 32 year old father was found to be homozygous for Gly1961Glu

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

CaseHPOFreeText: BCVA 20/70 and 20/80, atrophic zone of outer retinal and RPE atrophy, Bull's Eye Maculopathy, Macular atrophy

CaseNotHPOs: N/a

CaseNotHPOFreeText: N/a

Genotyping Method: Whole genome 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: CA119132, CA203216

SupplementalData: N/a

PMID: 26527198

Gene: ABCA4

HGNCID: HGNC:34

PMID: 23776498

Gene: ABCA4

Disease: Cone-Rod Dystrophy

PMID: 40401218

Gene: ABCA4

HGNC ID: 34

Annotating here since the article is a PDF.

This variant is mentioned in table 2 as a "disease associated mutation", but only as being present in the NBD/NBD interface. No further details are provided.

Case#: P3, male, 16yo at report, 9yo at dx, US with Indian ethnicity

DiseaseAssertion: Stargardt

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: BCVA (logMAR)= OD=20/160 (0.90), OS=20/125 (0.80)

CaseNotHPOs:

CaseNotHPOFreeText: ocular comorbidities such as diabetic retinopathy, uveitis, or glaucoma

GenotypingMethod: "genetic testing"

PreviouslyPublished: n/a

Variant: c.2453G>A; c.4532C>A (p.Pro1511His)

ClinVar: 99135

CAID: CA227000

SupplementalData: table 1

This variant is listed in supplementary tables S2 and S3. Proband KN-187 is a "solved" patient, meaning the phenotype matches the genotype. Compound heterozygous (c.6290C>T p.P2097L; c.6445C>T p.R2149X) male with Stargardt disease- all that is provided.

Case#: MD-0790, Spanish

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: "STGD1 was determined according to initial symptoms of VA loss; fundus images showing orange-yellow flecks in the retina, a beaten-bronze appearance; and normal or cone-altered ffERG results"

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Index cases were studied by different next-generation sequencing (NGS) strategies, including targeted gene panels, clinical exome, and/or whole-exome sequencing

PreviouslyPublished: n/a

Variant: c.1715G>C p.(Arg572Pro); c.4918C>T p.(Arg1640Trp)

ClinVar: 99073

CAID: CA226919

SupplementalData: Table S1

This variant was found in homozygosity 3 times in table S1 (Families MD-0991, MD-1164, and MD-1302). All with a STGD1 phenotype.

MD-0991 had onset of VA loss at 25yo, cone-rod pattern on ERG, and BCVA was 1.2/1.2. Segregation was mentioned, but no details provided.

MD-1164 had onset of VA loss at 42yo, no VF loss, and BCVA was 0.2/0.3. Segregation was not mentioned.

MD-1302 had no clinical details available.

GenotypingMethod: Index cases were studied by different next-generation sequencing (NGS) strategies, including targeted gene panels, clinical exome, and/or whole-exome sequencing

PMID:328843395

Gene: ABCA4

HGNC ID: 34

**Case#: ** Female, 35yo

FamilyInfo: Unremarkable

CasePresentingHPOs: HP:0000529 Progressive visual loss, HP:0030532 Visual acuity, HP:0007401 Macular atrophy

CaseHPOFreeText: 35-year-old woman presented with symptom of gradually progressive diminution of vision in both eyes since childhood. Patient gave no history of defective night vision.

CaseNotHPO n/a

GenoTypeMethod: n/a (optical coherence tomography (OCT))

This variant is mentioned as being on 8 individual alleles in Spanish families from a previous publication (PMID: 19028736)

This variant is found in compound heterozygosity with c.3386G>T p.(Arg1129Leu) in family MD-0723 in this study. Proband is 13yo at onset of VA loss and VF loss with night blindness. 15yo at opthalmological exam. Cone pattern on ERG. BCVA=0.2/0.2. Eligible for PP4.

PMID: 8533764

Gene: ABCA4

Disease: STGD

Supplemental Table 1. Patient WHP103 has this variant in compound heterozygosity with c.4720G>T(p.E1574*). Cannot confirm this is not the same proband as in PMID 31674661 since both have the same genotype and are of Chinese ancestry

PMID: 32036094

Gene: ABCA4

Disease: IRD

Case#: RP3.03, 23yo, 21yo on set, Moroccan

DiseaseAssertion: Retinitis Pigmentosa (RP19)

FamilyInfo: Born into a consanguineous family, parents are unaffected, has five unaffected siblings

CasePresentingHPOs: HP:0000505, HP:0007675, HP:0001133, HP:0007994, HP:0007843, HP:0000510, HP:0000580, HP:0007703

CaseHPOFreeText: Abnormal epiretinal membrane formation, Altered ERG traces, rod and cone photoreceptor dysfunctions, hyper fuorescence ring surrounding macula and peripheral retina, absence of cystic spaces

CaseNotHPOs: HP:0000551

CaseNotHPOFreeText: Central vision loss

Genotyping Method: Genomic DNA was extracted using QIAamp DND Blood Mini Kit, DNA underwent WES by BGI Tech Solutions, DNA was captured by MGIEasy Exome Capture V4 Probe Set, then Alligned using the Burrows-Wheeler Aligner and HaplotypeCaller of GAWK

PreviouslyPublished: CRB1, PDE6B

Variant: c.5908C>T, c.6148G>C

ClinVar: 7892, 7884

SupplementalData: Clinical data (table 1, figure 5), Genetic analysis (table 2), Patient Pedigree (figure 1.)

PMID: 31819343

Gene: ABCA4

HGNC ID: 34

PMID: 40465261

Gene: ABCA4

HGNC ID: 34

PMID: 37852949

Gene: ABCA4

Disease:

PMID: 29386879

Gene: ABCA4

Disease: ABCA4-associated retinal degenerations

Case#: QT959, Chinese

DiseaseAssertion: Cone-rod dystrophy

FamilyInfo: no pedigree provided for this family in this paper

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: 23776498-more phenotype information available there

Variant: c.[1957C > T];[4605insT] on WES

ClinVar: n/a

CAID: CA645372205

SupplementalData: n/a

PMID: 10746567

Gene: ABCA4

Disease: Stargardt

This paper appears to no longer be available even through the UNC library

Case#: 34 y.o female proband, caucasian(German), diagnosed with Stargardt, late onset.

DiseaseAssertion: STGD

FamilyInfo: Unaffected father, mother exhibiting retinal disease. Biparental history of glaucoma and AMD, pattern dystrophy on maternal side.

CasePresentingHPOs:HP:0001129, HP:0007722 ,HP:0007663, HP:0030329, HP:0007814, HP:0000608

CaseHPOFreeText: Proband exhibits retinal thinning in all retinal layers, alongside chorioretinal atrophy. Experienced increased central vision loss over the course of a decade. At time of study, diagnosed with Stargardt disease. Visual acuity 20/200 in right eye and 20/40 in left. Additionally found granular molting of retinal pigment epithilium.

CaseNotHPOs:n/a

CaseNotHPOFreeText:n/a

Genotyping Method: WES and variant calling performed at Columbia Institute for Genomic Medicine.

PreviouslyPublished:n/a

Variant: rs61751407, c.5714+5G>A

ClinVar: 432057

CAID: n/a

SupplementalData: n/a

This paper is listed under the ClinVar citations for this variant, but only as a paper that references other variants in the initiator codon that have been observed in individuals with ABCA4-related conditions. The actual initiator variant included in this paper is c.1A>G

PMID:39917552

Gene: ABCA4

HGNC ID: 34

PCMID:*PMC12657203

PMID41323838

Gene: ABCA4

HGNC ID: 34

Case#:80 year old man,

DiseaseAssertion:NA

FamilyInfo:NA

CasePresentingHPOs:NA

CaseHPOFreeText:Diagnosed w/ targardt disease at the age of 18 years, medical retierment at 64 as result

CaseNotHPOs:*parkinsons at 80

CaseNotHPOFreeText:NA

Genotyping Method:NA

PreviouslyPublished:NA

Variant:after gentic testing (unspecified) a pathogenic heterozygous mutation (G1961E) in ABCA4 gene a substiution, GAA) at amino acid position 1961, or c.5882 G>A at the complementary DNA level, or pGly1961Glu or G1961E at the protein level. No second mutation was identified. One of his 2 sisters had the same mutation.

ClinVar:NA

CAID:NA

SupplementalData:this goes into how eye retina transplant results and outcomes.

Case#: a 12-year-old female admitted to the B Department Hédi Raies institut of Ophtalmology in Tunis, Tunisia

DiseaseAssertion: Cone rod dystrophy

FamilyInfo: No parental consanguinity nor pathological or opthalmological history in the family

CasePresentingHPOs: HP:0000529, HP:0000662, HP:0001141, HP:0000543,HP:0007737, HP:0030602

CaseHPOFreeText: progressive visual loss, poor night vision, 1/20 visual acuity in both eyes, pallor of the optic disk, attenuated retinal vessels, paravascular bone spiculed pigmentations and an epimacular membrane, paravascular and macular heterogeneous hypoautofluorescence, diffuse alteration of ellipsoid zone, decreased photopic and scotopic responses.

CaseNotHPOs: NR

CaseNotHPOFreeText: NR

Genotyping Method: Whole exome sequencing, Sanger sequencing

PreviouslyPublished: NR

Variant: c.885delC, NM_000350.3

ClinVar: 438109

CAID: CA958684

SupplementalData: Karyotyping showed monosomy 45,X in the patient

PMID: 28600779

Gene: ABCA4

HGNCID: HGNC:34

MonDO:

Case: 16N-0520, Male, Saudi Arabia, 1 yo

DiseaseAssertion:

FamilyInfo: Consanguineous parents, positive family history

CasePresentingHPOs: HP:0000618, HP:0000648 (Blindness, Optic atrophy)

CaseHPOFreeText: Coloboma of eye

GenotypingMethod: WES, analysis of Vision Panel, constituent genes are described in PMID 26112015.

SupplementalData: Supplemental table

Variant: ABCA4:NM_000350:exon49:c.6764G>T:p.S2255I

CAID: CA202970

gnomAD: 0.4845 (gnomAD v4.0.0, Grpmax Filtered AF African/African-American) https://gnomad.broadinstitute.org/variant/1-93996161-C-A?dataset=gnomad_r4

VariantEvidence: Authors classified as VOUS. But later downgraded to LB in PMID 31130284.

Case#: Case #3483, likely European, 10yo at onset

DiseaseAssertion: ABCA4 disease

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText: foveal sparing

GenotypingMethod: NGS, Sanger

PreviouslyPublished: n/a

Variant: c.2453G>A (p.Gly818Glu); c.4462T>C (p.Cys1488Arg)

ClinVar: 99135

CAID: CA227000

SupplementalData: supplemental table 1

Case#: STGD47/164, 10-14yo 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

Case#: Patients #33 and 34, female, 63 and 61yo at report, respectively, German

DiseaseAssertion: ABCA4-related retinopathy

FamilyInfo: n/a but they could be related

CasePresentingHPOs:

CaseHPOFreeText: "Inclusion criteria comprised the presence of at least one disease-causing mutation in ABCA4 and a phenotype consistent with ABCA4-related retinopathy, including RPE atrophy and flecks." BCVA [LogMAR] for patient #33: OD= 0.4, OS= 0.1. BCVA [LogMAR] for patient #34: OD= 1.5, OS= 1.0. Reduced (over 2 SD) photopic B-wave and 30-Hz flicker amplitudes

CaseNotHPOs:

CaseNotHPOFreeText: Insufficient pupil dilation, additional retinal pathology, previous vitreoretinal surgery, or other ocular comorbidities substantially affecting visual function (e.g., significant media opacity, amblyopia, or optic nerve disease) led to exclusion. Abnormal responses on scotopic and photopic full-field ERG

GenotypingMethod:

PreviouslyPublished: likely the same patients as other Muller papers in this curation

Variant: c.3468C>G p.(Tyr1156*) and c.5059A>T p.(Ile1687Phe)

ClinVar: n/a

CAID: CA341290648

SupplementalData: Table S1 has genotype/phenotype info for probands

Case#: Sporadic Case #15, Mexican

DiseaseAssertion: Stargardt

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: STGD diagnosis based on: "onset of symptoms in childhood or early adulthood (before 20 years of age), bilateral central vision loss (central and peripheral visual field computerized testing), a retinal “beaten-bronze” foveal appearance and/or yellow-whitish flecks from the posterior pole to the mid periphery, normal caliber of the retinal vessels, no pigmented bone spicules in the retinal periphery, a normal to subnormal electroretinogram, and a typical dark choroid in fluorescein angiography."

CaseNotHPOs:

CaseNotHPOFreeText:

PreviouslyPublished: n/a

Variant: allele 1: c.6221G>T (p.G2074V) allele 2: c.2453G>A (p. G818E); direct sequencing of exons of ABCA4

ClinVar: 99135

CAID: CA227000

SupplementalData: n/a

PMID: 33301772

Gene: ABCA4

Disease: retinal dystrophy

Case#: Patient 8541, male, 10yo at presentation, 9yo at onset

DiseaseAssertion: Stargardt

FamilyInfo: n/a

CasePresentingHPOs:

CaseHPOFreeText: The inclusion criteria for patients were as follows: (1) clinical phenotypes were consistent with retinal dystrophy, and two or more ABCA4 gene mutations were identified by genetic analysis; or (2) clinical phenotypes were consistent with Stargardt disease, and one ABCA4 gene mutation was identified. The diagnosis of STGD was based on visual acuity loss with an atrophic maculopathy with or without yellowish-white flecks. BCVA= 0.92 OU. FAF type 1 ( a localized low FAF signal at fovea surrounded by a homogeneous background with or without perifoveal foci of high or low signal)

CaseNotHPOs:

CaseNotHPOFreeText: Yellowish-white flecks

GenotypingMethod: Analysis by targeted panel sequencing of 256 known retinal disease genes or by clinical exome sequencing of 1651 inherited eye disease-related genes

PreviouslyPublished: n/a

Variant: c.2587_2587+6delGG TAAGC; c.3468C>G p.(Tyr1156*)

ClinVar: n/a

CAID: CA341290648

SupplementalData: supplemental table S2

PMID: 34513887

Gene: ABCA4

HGNC ID: 34

Case#: Patient #9, Canadian

DiseaseAssertion: Stargardt

FamilyInfo: n/a

CasePresentingHPOs: "Clinical diagnosis of STGD was made when the patient, usually a child, developed central visual acuity loss with an atrophic maculopathy with or without flecks." No individual details

CaseHPOFreeText: n/a

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

PreviouslyPublished: n/a

Variant: c.6383 A>G p.(H2128R); c.785 G>A p.(G1961E)

ClinVar: 99455

CAID: CA227399

SupplementalData: info found in table S2

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

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

PMID: 11017087

Gene: ABCA4

Disease: retinopathies

Case#: Fujinami Patient 20, British

DiseaseAssertion: ABCA4-Related Retinal Disease

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: Dx of ABCA4-associated retinal disease. At least localized low AF signal at the fovea surrounded by a homogeneous background, but no specific information provided

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: ABCA4 microarray, PCR-enrichment–based next-generation sequencing (NGS) of ABCA4. Identified variants were confirmed by Sanger sequencing and assessed for pathogenicity by in silico analysis.

PreviouslyPublished: n/a

Variant: c.3208_3209insGT (p.S1071fs) ; c.1519G>T (p.D507Y) not confirmed in trans

CAID: CA958508

SupplementalData:

Case#: Patient on line 28, US

DiseaseAssertion: retinitis pigmentosa (RP)

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText:

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: Thirty-two of the most common disease-causing ABCA4 variations were selected for the initial screen. The entire research cohort was assayed for these 32 variations using a combination of SNPlex, SSCP analysis, TaqMan and automated DNA sequencing. All CRD and RP patients who had one plausible disease-causing allele identified in the first tier of screening were assayed by automated sequencing of the entire coding region of the ABCA4 gene in an effort to identify their second disease-causing allele. In addition, Stargardt patients who had one of the three most common alleles (Gly863Ala, Gly1961Glu or IVS38-10) were also sequenced through the entire coding region of the ABCA4 gene.

PreviouslyPublished: n/a

Variant: c.6601_6602del (p.Arg2201AlafsTer?) "Glu2200del2 aggGA"; c.5461-10T>C "IVS38-10 T>C"

CAID: CA227421

SupplementalData: genotype in supplemental table 1

PMID: 34440443

Gene: ABCA4

Disease: Retinal Dystrophies

PMID: 24317291

Gene: ABCA4

Disease: Stargardt

Case#: Patient #14, female, 34yo

DiseaseAssertion: Stargardt

FamilyInfo:

CasePresentingHPOs:

CaseHPOFreeText: stage 3, BCVA: OD=20/200 OS=20/250, fundus findings: OU: Severe RPE and choroidal atrophic changes in macula and throughout posterior pole and midperiphery, flecks throughout posterior pole, full field ERG: Subnormal rod, subnormal cone,

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: direct sequencing of the ABCA4 gene

PreviouslyPublished:

Variant: Compound heterozygous: G818E and C1488R

ClinVar:

CAID:

SupplementalData:

another case with 541 variant potentially not in cis with 1038

This paper was listed under this variant in LOVD, but I cannot find it in the main text or supplemental documents.

PMID: 16103129

Gene: ABCA4

Disease: severe retinal dystrophies

Case#: Family AR197 Proband 05, male, 7yo at onset

DiseaseAssertion: arRP

FamilyInfo: parents are het carriers, sibling (06) is affected and has the same genotype

CasePresentingHPOs:

CaseHPOFreeText: "diagnosed by clinical criteria (44) consistent with international standards and confirmed by review of ophthalmic records and retinal photographs. The clinical criteria included visual impairment at early age, progressive loss of peripheral visual functions and typical retinal changes of vascular attenuation, disc pallor and bone spicule accumulation." CF 3 feet OD; CF 2 feet OS

CaseNotHPOs:

CaseNotHPOFreeText:

GenotypingMethod: microarray chip, ABCR-400, PCR

PreviouslyPublished: n/a

Variant: [L541P; A1038V] and[L541P; A1038V]

ClinVar: 99067

CAID: CA226911

SupplementalData: n/a

ATPase activity in COS7 cells showed decreased activity (68.1% of wild-type), indicating that this variant impacts protein function (PS3_Supporting; PMIDs). However, this is not a cell type that is counted for PS3 evidence by the ABCA4 VCEP.

Case#: Patient 9, female, Mexican, symptoms onset 6 yrs. ago, Mexico City

DiseaseAssertion: IRD

FamilyInfo: parents are non-sanguineous and asymptomatic, they also denied any history related to ocular diseases. Information disclosed that the mother had one stillbirth and three miscarriages, but denied any related diseases/health issues to this child.

CasePresentingHPOs: HP:00305, HP:00080, HP:0000493, HP:0025586, HP:0030329, HP:0012713

CaseHPOFreeText: Proband presented with light sensitivity as well as adaptation difficulties when going from dark-to-light. Right eye was 20/200 and left eye was 20/160 from the visual acuity test. Macular bull's eye appearance. Subnormal rod and cone responses. Peripapillary sparing retina.

CaseNotHPOs: HP:0007737, HP:0000750, HP:0000510

CaseNotHPOFreeText: No afferent pupillary defect. No anomalies in anterior segment.

Genotyping Method: QIAamp DNA Blood Kit was used to extract gDNA and quantification/purity of the sample was found using a NanoDrop 2000 spectrophotometer. 293 genes were sequenced. gDNA was sequenced via Illumina technology. Following, certain sequences were additionally analyzed against a reference genome in order to identify changes and interpret.

PreviouslyPublished: n/a

Variant: NM_000350.3(ABCA4):c.4926C>G (p.Ser1642Arg), NM_000350.3(ABCA4):c.5044_5058del (p.Val1682_Val1686del)

ClinVar: 99332, 99340

CAID: n/a

SupplementalData: Phenotype data in results section as well as figures 1, 2, and 3 showing phenotypic testing results.

This individual appears to be the same as in PMID: 23755871. Same author in both papers

PMID: 33214501

Gene: ABCA4

Disease: ABCA4-Related Retinopathy

PMID: 19074458

Gene: ABCA4

Disease: cone-rod dystrophy

Case#: a 46-year-old male

DiseaseAssertion: Stargardt Disease

FamilyInfo:visual acuity loss by his brother and father

CasePresentingHPOs: HP:0007663

CaseHPOFreeText: visual acuity measured 20/400 bilaterally

CaseNotHPOs: NR

CaseNotHPOFreeText:NR

Genotyping Method: ABCA4 microarray (ABCR5000 chip)

PreviouslyPublished: NR

Variant: c.5714+5G>A

ClinVar: 99403

CAID: CA227338

SupplementalData:NR

PMID:18854780

Gene: ABCA4

HGNC ID: 78

Disease: Stargardt

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

PMID: 20163366

Gene: ABCA4

HGNC ID: 34

Case#: single case, 37-year-old male, ethnicity not specified although family originally from the Middle East, examined in the UK

DiseaseAssertion: STGD

FamilyInfo: No history of consanguinity. No history of inherited retinal disease, poor vision or colour vision disturbance. Father had recent diagnosis of chronic central serous retinopathy, not consistent with STGD

CasePresentingHPOs: n/a

CaseHPOFreeText: Late-onset Stargardt disease with slowly progressive phenotype. The patient present with a 3-year history of decreased vision in the right eye that had recently significantly worsened. Visual acuity was 6.24 in right eye and 6/6 in left eye. Fundus examination reveled scattered atrophy and pisiform fundal flecks in both eye, right worse than left. Fluorescein angiography showed a silent choroid and partial bull's eye maculopathy, right worse than left. OCT showed loss of photoreceptors in both eyes and partial central sparing in the left eye. Photopic and scotopic ERG showed reduced amplitude of responses in the right eye and lower range amplitudes in the left eye, normal implicit times in both eyes. Pattern ERG and multifocal ERD showed central retinal dysfunction with preserved peripheral function. No change in vision or retinal appearance over the next 14 months of follow up.

CaseNotHPOs: n/a

CaseNotHPOFreeText: No night vision symptoms. No history of retinotoxic drug exposure.

Genotyping Method: Next-generation sequence analysis with the Oxford Genetics Testing Laboratory Macular Gene Panel.

PreviouslyPublished: Thr829Met missense mutation had been previously reported in an individual with autosomal recessive retinitis pigmentosa, but not previously associated with STGD phenotype.

Variant: ABCA4 NM_000350 c.5882G>A, p.(Gly1961Glu) c.2486C>T, p.(Thr829Met)

ClinVar: n/a

CAID: CA958261, CA119132

SupplementalData: n/a

PMID:39215425

Gene: ABCA4

HGNC ID: 34

Case#:1 this ia family but the 20 year old son is the firs tone spoken about a herdirtary eye disease, shows phenotype for years till syptmos worsned with age

DiseaseAssertion: Table 1 The summary of the clinical assessment of IRD patients’ family in this research fro there down they did a whole pannel on the family

Pedigree one can be fore form the beggginnings of case presention section?

CasePresentingHPOs: suffered from tunnel vision and blurry night vision began 13 years ago

CaseHPOFreeText:NA

CaseNotHPOs:NA

CaseNotHPOFreeText:NA

Genotyping Method:NA

PreviouslyPublished:NA

Variant:NA

ClinVar:

CAID:NA

SupplementalData:NA

Inheritance pattern Autosomal Recessive

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: 27208204

Gene: ABCA4

Disease: IRD

PMID: 32627976

Gene: ABCA4

HGNC ID: 34

Case#: Patient 1, Female, age 40

DiseaseAssertion: STGD1

FamilyInfo: n/a

CasePresentingHPOs: HP:0007722, HP:0000608, HP:0000007

CaseHPOFreeText: Patient diagnosed with STGD type 1, presenting with retinal pigment atrophy as well as other symptoms typical of STGD1 with reduced visual acuity. Patient daignosed at age 16.

CaseNotHPOs: n/a

CaseNotHPOFreeText: n/a

Genotyping Method: Patient ABCA-4 gene sequenced via Sanger sequencing of all 50 exons, Splice variants were identified by synthesized cDNA from RNA isolation with RT-PCR analysis with exonic primers.

PreviouslyPublished: Variant 1 identified in association with retinal dystrophy in these PMC articles: 23982839, 25082829, 25082885, 28327576

Variant: NM_000350.3(ABCA4):c.859-9T>C, NM_000350.3(ABCA4):c.303-3C>G

ClinVar: 3249248, 859348

gnomAD total allele frequency: 0.005% of var . 1

CAID: n/a

SupplementalData: Fig 1: Minigene RNA analysis of splice variants. A: genomic region of exon 40 on ABCA-4. B: genomic regions of exons 39-41 to investigate specific variant:oncanonical splice site variant c.5714+5G>A Fig 2: overview of wild-type midigene splice constructs of ABCA-4 and locations of 47 different non canonical splice site variants Fig 3: Overview of splice defects from nine different non canonnical splice variants in ABCA-4 gene. Fig 4: percentages of normal ABCA-4 transcripts as a result of noncanonical splice variants using electrophoresis system analysis. Table 1: Non canonical splice variants and observed protein affects.