414 Matching Annotations
  1. Sep 2026
    1. Patient 1 is 44 years old and presented in 1991 aged 23 with deteriorating central vision and visual acuity (VA) of 6/36 in the right eye and 6/60 in the left. Fundus photography in 1994 identified bilateral numerous yellowish-white flecks at the posterior pole (Fig. 1). In 2003, her VA was 6/60 in each eye, with bilateral macular atrophy surrounded by flecks (Fig. 1). Autofluorescence (AF) imaging in 2005 detected a localized low signal at the macula with numerous foci of abnormal signal (Fig. 1). By 2008, the macular atrophy had enlarged and flecks were less apparent.

      Case#: Female, age 44 years old

      DiseaseAssertion: Discordant STGD phenotype

      FamilyInfo: Information revolving the sister of this patient is given as well as they both have a discordant STGD phenotype. Additionally, it mentions that the parents each harboured a mutation but were asymptomatic/had normal examination results.

      CasePresentingHPOs: HP:0001141, HP:0007401, HP:0030602

      CaseHPOFreeText: At 23 central vision was deteriorating and patient had a VA of 6/36 in the right eye and 6/60 in the left. Through fundus photography, bilateral yellow/white flecks were found at the posterior pole. 12 years later, her VA was retested and it was 6/60 in both eyes. After autofluorescnece (AF) imaging was done, there was localized low signal at the macula found with abnromal foci. In 2008 her macular atrophy had enlarged and the flecks were less apparent.

      CaseNotHPOs: N/a

      CaseNotHPOFreeText: In this article there was not a phenotype presented that was normal.

      CasePreviousTesting: It mentioned that there were two previously reported variants on the same allele detected in the siblings and one unique novel variant on the second allele for this patient. However, the testing they used was not listed, it just stated that the variants were found through sequencing. For this patient the variants were p.L541P/p.A1038V and p.R881C.

      GenotypingMethod: Just mentioned sequencing and ABCA4 screening to look for two variants p.L541V and p.A1038V and a third novel variant p.R881C.

      PreviouslyPublished: N/a

      Variant: 1) NM_000350.3(ABCA4):c.1622T>C (p.Leu541Pro) 2) NM_000350.3(ABCA4):c.3113C>T (p.Ala1038Val) 3) N/a

      ClinVar ID: 1) 99067 2) 7894 3) N/a

      **CAID: ** 3) Because there was not a reference or alternate allele provided in this article I was unable to find a CAID for p.R881C.

      gnomAD: 1) Highest minor allele frequency was 0.00017 (https://www.ncbi.nlm.nih.gov/clinvar/variation/99067/) 2) Highest minor allele frequency was 0.00188 (https://www.ncbi.nlm.nih.gov/clinvar/variation/7894/) 3) N/a

      SupplementalData: Figure 1 had information regarding imaging and other testing done on the patient that is vital for phenotypic characterization. Also, it mentions a variant known as p.R881C, but was unable to find anything on ClinVar or gnomAD.

    1. We report an 11-year-old girl

      Case#: 11 year old female

      DiseaseAssertion: Stargardt’s Disease

      ParentalTesting: She was the product of an uncomplicated pregnancy born to a healthy Filipino mother and Italian/Irish father with no known family history of ocular disease. The mother and father were asymptomatic but not examined. Segregation analyses showed that both parents are asymptomatic carriers.

      CasePresentingHPOs: HP:0007754, HP:0011462, HP:0008035

      CasePhenotypeFreeText: The ABCA4 gene, when mutated, results in a spectrum of retinal degeneration, including Stargardt macular dystrophy, fundus flavimaculatus, autosomal recessive retinitis pigmentosa, and cone-rod dystrophy (1). Over 800 disease-associated ABCA4 gene mutations have been reported.

      CaseNotHPOs: N/A

      CaseNotPhenotypeFreeText: N/A

      CasePreviousTesting: The proband underwent a full consultative ophthalmic examination at the Ocular Genetics Clinic at Wills Eye Hospital, including visual acuity, slit-lamp, and dilated fundus examination. Fundus autofluorescence and spectral-domain optical coherence tomography (Spectralis; Heidelberg Engineering), Goldmann visual field (Octopus 900 perimeter; Haag-Streit International), and intravenous fluorescein angiography were obtained. Full-field electroretinogram (Espion; Diagnosys LLC) and multifocal electroretinogram (Veris V.6.4.3; EDI Inc.) were performed in accordance with the International Society of Clinical Electrophysiology and Vision standards. Best-corrected visual acuity was 20/125 in the right eye and 20/200 in the left eye. The patient demonstrated eccentric fixation. Pupillary responses were normal. Slit-lamp examination was normal. Fundus examination revealed healthy optic nerves and retinal blood vessels, bilateral macular geographic pigmentary stippling with subretinal flecks in and around this area, and a blunted internal limiting membrane reflex (Fig. 1). Peripheral retina was normal.

      GenotypingMethod: Genotyping microarray chips for ABCA4 can identify >98% of the most common mutations. In this report, we describe 2 novel ABCA4 variants in a patient with Stargardt disease. Bioinformatic and in silico analysis of the functional consequences of these variants provided compelling evidence for pathogenicity.

      Variant: c.850_857delATTCAAGA and c.6184_6187delGTCT

      CAID: CA10604079 and CA10604078

      MultipleGeneVariants: N/A

      PreviouslyPublished: N/A

      AdditionalInfo: Bioinformatic assessment of the c.850_857delATTCAAGA mutation showed that it resulted in a truncated 317 amino acid polypeptide, devoid of several essential domains of the ABCA4 transporter. The c.6184_6187delGTCT mutation led to a premature stop codon at the C-terminal end of the protein, resulting in a loss of a total of 161 amino acid residues. Although less than 7% of the protein was absent, the important VFVNFA motif, present within the last 30 amino acids of the NBD2 domain, was deleted (Fig. 2). This motif is known to be critical to ABCA4 protein function, is highly conserved among members of the ABCA transporter subfamily, and has also been linked to Tangier disease in the ABCA1 protein (9). Removal of this motif in ABCA4 leads to a loss of retinal stimulated ATPase in vitro and energy transduction of the transporter (9, 10). Protein modeling predicted a loss of an essential β-sheet, which significantly altered its structure. The NBD domains are sites of ATP hydrolysis that provide energy for transport of R-PE through rod outer segment membranes. Enzymatic studies suggest that the NBD2 domain in particular provides energy necessary for translocation of retinal derivatives generated in the visual cycle. The structural changes in NBD2 would affect ABCA4 transporter’s ability to transport retinoids, leading to accumulation of cytotoxic lipofuscin in RPE cells and ultimately photoreceptor cell death.

    1. Case 3: RP3.03

      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.)

    1. A 37-year-old man presented with a 3-year history of decreased vision in the right eye, which had recently become worse.

      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

    1. 48-year-old woman

      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)

    1. The proband (K206–2) was 25-years-old

      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

    1. ABCA4

      Case#: 1 male, 6 years old, from Taiwanese and Korean decent.

      DiseaseAssertion: ABCA4-related retinopathy Stargardt disease

      FamilyInfo: Single affected individual. Paternal uncle presented with Stargart disease previously, and Taiwanese and Korean descent underwent genetic testing to identify two pathogenic variants in the ABCA4 gene. One of the variants found was the same ABCA4 variant from the originally affected individual. No additional family information is provided in text.

      CasePresentingHPOs: HP:0000529 - progressive visual loss, HP:0025010 - Foveal atrophy, HP:0000603 - Central scotoma, HP:0007663 - Decreased visual acuity, HP:0030602 - Abnormal fundus autofluorescence imaging, HP:0007984 - ERG: Reduced dark-adapted b-wave amplitude, HP:0000512 - Abnormal electroretinogram, HP:0020032 - Hyperreflective retinal dots on OCT

      CaseHPOFreeText: peripapillary sparing was observed on fundus autofluorescence imaging.

      CaseNotHPOs: HP:0012045 - Retinal flecks

      CaseNotHPOFreeText: N/A

      Genotyping Method: Genetic testing was used and after sequencing two variants were found on the ABCA4 gene.

      PreviouslyPublished: N/A

      Variant: NM_000350.3(ABCA4):c.3523-2A>G

      Variant: NM_000350.3(ABCA4):c.2249T>C (p.Leu750Pro)

      ClinVar: Variation ID: 866764

      ClinVar: Variation ID: 417984

      CAID: N/A

      SupplementalData: N/A

    1. 10-year-old girl

      Case#: Patient female, 10y, ethnicity not reported

      DiseaseAssertion: Stargardt disease (STGD1), early onset

      FamilyInfo: autosomal recessive inheritance; co-segregation of variants in parents (each heterozygous). Pedigree shown in Figure 1A. One unaffected sibling reported.

      CasePresentingHPOs: HP:0007663, HP:0007754, HP:0002587, HP:0030636, HP:0000548

      CaseHPOFreeText: early-onset visual decline (age 7), symmetric disease in both eyes, hyperautofluorescent ring surrounding macular atrophy, lipofuscin accumulation, photoreceptor degeneration.

      CaseNotHPOs: HP:0007707

      CaseNotHPOFreeText: normal anterior segment on slit lamp exam; no external ocular abnormalities reported.

      Genotyping Method: Sanger sequencing confirmation; variant identification likely via next-generation sequencing (not explicitly stated).

      PreviouslyPublished: n/a

      Variant: ABCA4 NM_000350.2: c.6817-713A>G; c.3259G>A (p.Glu1087Lys)

      ClinVar: n/a

      CAID: CA2837995439, CA227097

      SupplementalData: phenotype and validation data in Figures 1–5 and Supplemental Figures S1–S5

    1. A 37-year-old East Asian woman

      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

    1. 024 m Caucasian STGD ABCA4 NM_000350.2 c.[6601_6602delAG];[=], c.[4253+43G>A];[=] p.Arg2201fs* p.Ile1377Hisfs*3 Not found 0.004694 AR Pathogenic Pathogenic 2 [36] [19]

      Case#: Patient 24, male, Caucasian, onset at 50yo, Germany

      DiseaseAssertion: STGD

      FamilyInfo: co-segregation of variant in 2 family members (siblings) but they do not appear to be affected based on pedigree

      CasePresentingHPOs: HP:0030528, HP:0000505, HP:0012508, HP:0001105, HP:0025148

      CaseHPOFreeText: progressive paracentral scotoma OU, progressive visual impairment OU (blurry vision). BCVA: OD-0.1, OS-0.22. Tension: 13mmHg/14mmHg. FAF: bilateral hyperautofluorescent macular and peripapillary spots, few spots of paracentral retinal atrophy (foveal sparing). Autofluorescence and deposits (severity): deposits medium, atrophy low. OCT: hyperreflective spots, partially invading into the outer retina, partly confluent lesions of cRORA, foveal sparing, degenerative intraretinal fluid. Central macular thickness: 328µm/322µm. Macular volume: 9.31mm³/9.00mm³. mfERG: bilateral amplitudes in normal range, slight relative reduction in the paracentral areas. Fluorescein angiography: bilateral dark choroid, mild paracentral dye pooling in the late phase. Color vision: Inconspicuous. Clinical examination: pattern-like distribution of the lesions.

      CaseNotHPOs: n/a

      CaseNotHPOFreeText: n/a

      GenotypingMethod: WES, in-house RD-associated gene panel including 619 candidates and disease-associated genes

      PreviouslyPublished: n/a

      Variant: ABCA4 NM_000350.2 c.[6601_6602delAG] (p.Arg2201fs);[=], c.[4253+43G>A] p.Ile1377Hisfs3;[=]

      CAID: CA227421; CA227172

      SupplementalData: phenotype and segregation info in supplemental data (table s1, figure s1)

    1. ABCA4 gene mutation

      Case#: 1 female, 12 years old.

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

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

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

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

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

      CaseNotHPOFreeText: Relatively normal foveal architecture.

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

      PreviouslyPublished: N/A

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

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

      CAID: N/A

      SupplementalData: N/A

  2. Jul 2026
    1. Table 2.

      Case#:Not assigned

      DiseaseAssertion:MPS type I with evidence of cognitive impairment defined as a score of at least 1 SD below mean on IQ testing or in one domain of neuropsychological function; attenuated MPS I

      FamilyInfo:No information

      CasePresentingHPOs:HP:0100543

      CaseHPOFreeText:

      CaseNotHPOs:HP:0032557

      CaseNotHPOFreeText:Subjects were excluded if they had undergone hematopoietic stem cell transplantation, were unable to comply with study procedures, had significant lumbar pathology precluding access to the intrathecal space via lumbar puncture, or significantly impaired spinal CSF flow as detected on a nuclear medicine flow study as part of screening.

      CaseEnzymeAssay:No information

      CaseUrineGAGs:No information

      CaseERT:Yes

      CaseBMT:No (exclusion criterion)

      Variant1:L238Q

      Variant1ClinVarID:265418

      Variant1CAID:

      Variant2:W402X

      Variant2ClinVarID:

      Variant2CAID:

      AdditionalVariants:N/A

      ParentalGenotype:Not specified

      PreviouslyPublished

    2. Table 2.

      Case#:Not assigned

      DiseaseAssertion:MPS type I with evidence of cognitive impairment defined as a score of at least 1 SD below mean on IQ testing or in one domain of neuropsychological function; attenuated MPS I

      FamilyInfo:No information

      CasePresentingHPOs:HP:0100543

      CaseHPOFreeText:

      CaseNotHPOs:HP:0032557

      CaseNotHPOFreeText:Subjects were excluded if they had undergone hematopoietic stem cell transplantation, were unable to comply with study procedures, had significant lumbar pathology precluding access to the intrathecal space via lumbar puncture, or significantly impaired spinal CSF flow as detected on a nuclear medicine flow study as part of screening.

      CaseEnzymeAssay:No information

      CaseUrineGAGs:No information

      CaseERT:Yes

      CaseBMT:No (exclusion criterion)

      Variant1:L238Q

      Variant1ClinVarID:265418

      Variant1CAID:

      Variant2:63delC

      Variant2ClinVarID:

      Variant2CAID:

      AdditionalVariants:N/A

      ParentalGenotype:Not specified

      PreviouslyPublished

    3. Table 2.

      Case#:Not assigned

      DiseaseAssertion:MPS type I with evidence of cognitive impairment defined as a score of at least 1 SD below mean on IQ testing or in one domain of neuropsychological function; attenuated MPS I

      FamilyInfo:No information

      CasePresentingHPOs:HP:0100543

      CaseHPOFreeText:

      CaseNotHPOs:HP:0032557

      CaseNotHPOFreeText:Subjects were excluded if they had undergone hematopoietic stem cell transplantation, were unable to comply with study procedures, had significant lumbar pathology precluding access to the intrathecal space via lumbar puncture, or significantly impaired spinal CSF flow as detected on a nuclear medicine flow study as part of screening.

      CaseEnzymeAssay:No information

      CaseUrineGAGs:No information

      CaseERT:Yes

      CaseBMT:No (exclusion criterion)

      Variant1:65delC

      Variant1ClinVarID:

      Variant1CAID:

      Variant2:H240R

      Variant2ClinVarID:947028

      Variant2CAID:

      AdditionalVariants:N/A

      ParentalGenotype:Not specified

      PreviouslyPublished