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  1. Last 7 days
  2. www.ajo.com www.ajo.com
    Genotype–Phenotype Correlations in a Spanish Cohort of 506 Families With Biallelic ABCA4 Pathogenic Variants
    1
    1. Vibhor 22 Aug 2026
      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

      Case#: MD-0242, onset at 18yo, 24yo at report

      DiseaseAssertion: STGD1

      FamilyInfo: Segregation noted, but no specific details provided

      CasePresentingHPOs:

      CaseHPOFreeText: VA loss, BCVA=0.1/0.1, "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: VF loss, abnormal ERG

      GenotypingMethod:

      PreviouslyPublished: n/a

      Variant: c.1715G>C p.(Arg572Pro); c.5242G>A p.(Gly1748Arg)

      ClinVar: 99073

      CAID: CA226919

      SupplementalData: Table S1

      SupplementalTable CAID:CA226919 ClinVarID:99073 CaseInfo Individual automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    ajo.com/article/S0002-9394(20)30323-8/fulltext
  3. Aug 2026
  4. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Clinical science: Frequency of ABCA4 mutations in 278 Spanish controls: an insight into the prevalence of autosomal recessive Stargardt disease
    1
    1. Vibhor 14 Aug 2026
      Of the 266 arSTGD chromosomes studied, mutations were identified in 161, resulting in a detection rate for the genotyping microarray of 60.5%: two mutant alleles were found in 64/133 patients (48.1%), whereas in 33/133 cases (24.8%) only one allele could be identified. A total of 56 different sequence variants related to the disease were identified, including missense (42), nonsense (four) frameshift (five) and splicing (five) mutations. Furthermore, combinations of variants acting in cis (complex alleles; six double alleles, one triple allele) were also found. Of this spectrum of substitutions, the p.Arg1129Leu (c.3386G>T) allele accounted for 26% of the disease-associated alleles (fig 2). Considering the percentage represented by this variant in patients (26%) and the obtained mutation detection rate (60.5%), this change would represent the 15.7% of all the potential arSTGD associated alleles.

      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

      PreviouslyPublished CAID:CA226919 ClinVarID:99073 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    ncbi.nlm.nih.gov/pmc/articles/PMC2743849/
  5. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Outcome of ABCA4 disease-associated alleles in autosomal recessive Retinal Dystrophies: Retrospective analysis in 420 Spanish families
    1
    1. Vibhor 11 Aug 2026
      MD-0242ABCA412c.1715G>Cp.Arg572ProNot detected18YesABCR400

      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:

      CaseInfo Individual ClinVarID:99073 CAID:CA226919 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    ncbi.nlm.nih.gov/pmc/articles/PMC3808491/
  6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    A YAC contig encompassing the recessive Stargardt disease gene (STGD) on chromosome 1p
    1
    1. Vibhor 10 Aug 2026
      Stargardt disease (STGD) and fundus flavimaculatus are infrequent autosomal recessive conditions characterized by a juvenile macular dystrophy and variable degrees of peripheral retinal changes. Linkage analysis performed in 47 STGD/fundus flavimaculatus families demonstrated significant linkage to 13 polymorphic DNA markers on chromosome 1p. The maximum combined two-point lod score was 32.7 (maximum recombination fraction [phi max] = .006) with the polymorphic marker D1S188. Our data demonstrate that STGD and fundus flavimaculatus are the same disorder clinically and genetically and provide further evidence for genetic homogeneity of this phenotype. Analysis of recombination events on disease chromosomes placed the STGD gene within a 4-cM interval between markers D1S435 and D1S236. A physical map was constructed of a YAC contig flanking STGD, from markers D1S500 to D1S495, and includes the critical interval delineated by historical recombinants. This contig spans approximately 31 cM, with one gap (3-5 cM) that is outside the 4-cM critical region. Localization of STGD to a single YAC contig will facilitate its positional cloning.

      Text is a PDF, but this paper is the previously published paper referenced in PMID: 9973280. Pedigree is found here

      PreviouslyPublished CAID:CA226919 ClinVarID:99073 FamilyInfo automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    pubmed.ncbi.nlm.nih.gov/8533764/
  7. www.ajo.com www.ajo.com
    Genotype–Phenotype Correlations in a Spanish Cohort of 506 Families With Biallelic ABCA4 Pathogenic Variants
    1
    1. Vibhor 05 Aug 2026
      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

      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

      CaseInfo Individual SupplementalTable ClinVarID:99073 CAID:CA226919 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    ajo.com/article/S0002-9394(20)30323-8/fulltext
  8. Jul 2026
  9. www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov
    Copy-number variation contributes 9% of pathogenicity in the inherited retinal degenerations
    1
    1. Vibhor 31 Jul 2026
      A cohort of 500 unrelated IRD patients was sequenced with the targeted NGS panel Genetic Eye Disease test (GEDi)3 and analyzed with a comprehensive approach, which included a standard NGS analysis pipeline detecting single-nucleotide variants (SNVs) and small insertions and deletions (indels),16 interrogation of sequence reads to detect the known pathogenic MAK-Alu insertion,21 and application of NGS read-depth algorithms (ExomeDepth15 and gCNV16) to detect larger deletions and duplications, or CNVs (Fig. 1). In this study we define CNVs as deletions or duplications that range from an average size of an exon (≈50–200 bp) and that are not detectable by standard NGS pipelines, to megabases of DNA.22

      Case#: OGI802_001554

      DiseaseAssertion: IRD

      FamilyInfo: n/a

      CasePresentingHPOs:

      CaseHPOFreeText:

      CaseNotHPOs:

      CaseNotHPOFreeText:

      GenotypingMethod: detection of CNVs on the panel-based NGS Genetic Eye Disease (GEDi) diagnostic test that involves sequencing the exons of all known IRD disease genes

      PreviouslyPublished: n/a

      Variant: c.1715G>C; c.5196+1137G>A

      ClinVar: 99073

      CAID: CA226919

      SupplementalData: Table S2

      SupplementalTable CaseInfo Individual CAID:CA226919 ClinVarID:99073 automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
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    ncbi.nlm.nih.gov/pmc/articles/PMC7272325/
  10. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov
    Genotype/Phenotype analysis of a photoreceptor-specific ATP-binding cassette transporter gene, ABCR, in Stargardt disease.
    2
    1. Vibhor 26 Jul 2026
      Mutation scanning and direct DNA sequencing of all 50 exons of ABCR were completed for 150 families segregating recessive Stargardt disease (STGD1). ABCR variations were identified in 173 (57%) disease chromosomes, the majority of which represent missense amino acid substitutions. These ABCR variants were not found in 220 unaffected control individuals (440 chromosomes) but do cosegregate with the disease in these families with STGD1, and many occur in conserved functional domains. Missense amino acid substitutions located in the amino terminal one-third of the protein appear to be associated with earlier onset of the disease and may represent misfolding alleles. The two most common mutant alleles, G1961E and A1038V, each identified in 16 of 173 disease chromosomes, composed 18.5% of mutations identified. G1961E has been associated previously, at a statistically significant level in the heterozygous state, with age-related macular degeneration (AMD). Clinical evaluation of these 150 families with STGD1 revealed a high frequency of AMD in first- and second-degree relatives. These findings support the hypothesis that compound heterozygous ABCR mutations are responsible for STGD1 and that some heterozygous ABCR mutations may enhance susceptibility to AMD.

      Annotating here since the full text is a PDF.

      Case#: Family AR321 proband, US, 6yo at onset

      DiseaseAssertion: Stargardt

      FamilyInfo: proband and two other siblings are affected

      CasePresentingHPOs: The essential and defining features of STGD were (1) pedigrees with at least one living affected individual compatible with autosomal recessive inheritance; (2) an ophthalmoscopically characteristic retinal disorder in families with both parents living; (3) bilateral central visual loss with both “beaten metal” elliptical foveal dystrophy and temporal pallor of the optic discs, documented by retinal color photography, with or without yellow-pigment epithelial flecks in the macular and/or retinal “near periphery”; and (4) the characteristic fluorescein angiographic feature of a dark choroid (Blacharski 1988).

      CaseHPOFreeText:

      CaseNotHPOs:

      CaseNotHPOFreeText: (1) evidence of autosomal dominant inheritance; (2) any history of night blindness, loss of peripheral vision, or "retinitis pigmentosa"; (3) cataracta complicata or cells in the vitreous; (4) substantially abnormal electroretinographic or electrooculographic responses; (5) no fluorescein angiography performed or no dark choroid documented; (6) neurological disease (including loss of cognition or seizures); 7) drug exposures (especially to antimalarial and agents known to cause crystalline retinopathies); or (8) any "atypical" maculopathies in which a unique diagnosis of STGD could not be established.

      PreviouslyPublished: PMID: 8533764

      Variant: c.3113C>T p.A1038V; c.1715G>C p.R572P . Heteroduplex and SSCP analyses were used to screen the 50 exons of ABCA4. Linkage analysis and haplotype analysis were previously performed

      ClinVar: 99073

      CAID: CA226919

      SupplementalData: n/a

      ClinVarID:99073 CAID:CA226919 CaseInfo Individual PreviouslyPublished automated_hgnc:34 automated_hgnc_source:CAID ClinGen ABCA4 Annotations
    2. Vibhor 09 Jul 2026
      Mutation scanning and direct DNA sequencing of all 50 exons of ABCR were completed for 150 families segregating recessive Stargardt disease (STGD1). ABCR variations were identified in 173 (57%) disease chromosomes, the majority of which represent missense amino acid substitutions. These ABCR variants were not found in 220 unaffected control individuals (440 chromosomes) but do cosegregate with the disease in these families with STGD1, and many occur in conserved functional domains. Missense amino acid substitutions located in the amino terminal one-third of the protein appear to be associated with earlier onset of the disease and may represent misfolding alleles. The two most common mutant alleles, G1961E and A1038V, each identified in 16 of 173 disease chromosomes, composed 18.5% of mutations identified. G1961E has been associated previously, at a statistically significant level in the heterozygous state, with age-related macular degeneration (AMD). Clinical evaluation of these 150 families with STGD1 revealed a high frequency of AMD in first- and second-degree relatives. These findings support the hypothesis that compound heterozygous ABCR mutations are responsible for STGD1 and that some heterozygous ABCR mutations may enhance susceptibility to AMD.

      Annotating here since the full text is a PDF.

      Case#: Family AR321 proband, US, 6yo at onset

      DiseaseAssertion: Stargardt

      FamilyInfo: proband and two other siblings are affected

      CasePresentingHPOs: The essential and defining features of STGD were (1) pedigrees with at least one living affected individual compatible with autosomal recessive inheritance; (2) an ophthalmoscopically characteristic retinal disorder in families with both parents living; (3) bilateral central visual loss with both “beaten metal” elliptical foveal dystrophy and temporal pallor of the optic discs, documented by retinal color photography, with or without yellow-pigment epithelial flecks in the macular and/or retinal “near periphery”; and (4) the characteristic fluorescein angiographic feature of a dark choroid (Blacharski 1988).

      CaseHPOFreeText:

      CaseNotHPOs:

      CaseNotHPOFreeText: (1) evidence of autosomal dominant inheritance; (2) any history of night blindness, loss of peripheral vision, or "retinitis pigmentosa"; (3) cataracta complicata or cells in the vitreous; (4) substantially abnormal electroretinographic or electrooculographic responses; (5) no fluorescein angiography performed or no dark choroid documented; (6) neurological disease (including loss of cognition or seizures); 7) drug exposures (especially to antimalarial and agents known to cause crystalline retinopathies); or (8) any "atypical" maculopathies in which a unique diagnosis of STGD could not be established.

      PreviouslyPublished: PMID: 8533764

      Variant: c.3113C>T p.A1038V; c.1715G>C p.R572P . Heteroduplex and SSCP analyses were used to screen the 50 exons of ABCA4. Linkage analysis and haplotype analysis were previously performed

      ClinVar: 99073

      CAID: CA226919

      SupplementalData: n/a

      ClinVarID:99073 CAID:CA226919 CaseInfo Individual PreviouslyPublished ClinGen ABCA4 Annotations hgnc_imputed:HGVS
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    pubmed.ncbi.nlm.nih.gov/9973280/