PMID: 29706639

Gene: ABCA4

HGNCID: HGNC:34

MonDO: MONDO:0019353

Bioinformatic analyses of an SQL-based database containing 12272 variants that appear in 178 IRD genes in 5706 individuals of Ashkenazi Jewish origin based on the gnomAD database (version 2) and variants that were published in the scientific literature that was extracted from HGMD. Authors extracted information regarding IRD variants from various sources (including data of 5706 Ashkenazi Jewish (AJ) samples and a large cohort of Israeli patients with IRDs) to estimate carrier frequency of IRD mutations in different subpopulations in Israel. Two major databases aiming to estimate carrier frequency of IRD mutations in the Israeli population (Fig. 1): “gnomAD-AJ-IRD DB” containing data of 5706 AJ controls extracted from gnomAD and “HW-IRD DB” containing data extracted from our cohort of Israeli patients with IRDs.

See Fig 2 for breakdown of variants analyzed.

The final DB (IRDB) (Fig. 1 and Table S7) includes all 399 variants from “gnomAD-AJ-IRD DB” and “HW-IRD DB” that were considered here as pathogenic mutations in 111 known IRD genes.

To establish the “HW-IRD DB” (Fig. 1), we collected data on Israeli IRD patients with a known cause of disease (a cohort of >2000 IRD families). The HW-IRD DB includes 289 pathogenic mutations (Fig. 1) that were identified in IRD patients who have biallelic variants.

SupplementalData: S7, carrier frequency data for each mutation in all nine studied subpopulations. Carrier frequency was calculated as 2pq where p = 1 − q and q was calculated as the root square of the number of homozygous patients plus half the number of compound heterozygous patients divided by the population size

Variant: NM_000350.2:c.4895dup,p.Asn1632fs

CAID: CA915941330

Case: Ashkenazi Jewish patient with inherited retinal disease, STGD, CRD

CasePresentingHPOs: HP:0000548 (Cone/cone-rod dystrophy, CRD)

CaseHPOFreeText: Stargardt disease (STGD)

PMID: 22334370

Gene: ABCA4

HGNC ID: 34

Disease: Retinitis Pigmentosa

PMID:35973334

Gene: ABCA4

HGNC ID: 34

Case#: the youngest sister II.7, aged 12 years, was the least affected

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: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: PMC6777736

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.

PMID: PMC6548695

Gene: ABCA4

HGNC ID: 34

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

PMID: 31766579

Gene: ABCA4

HGNC ID: 34

PMID:18854780

Gene: ABCA4

HGNC ID: 78

Disease: Stargardt

PMID: 38607040

Gene: ABCA4

HGNC ID: 34

PMID: 19352439

Gene: ABCA4

HGNC ID: 34

PMID: 31456290

Gene: ABCA4

HGNCID: HGNC:34

SupplementalData: as applicable Table S2. Variant found in cohort of 2,420 families including 3,413 individuals with inherited retinal diseases in Israel. Likely, this is the same family reported in PMID 29706639.

Total number of families: 1; phenotype/s: CRD; NM_000350.2:c.4895dup, p.(Asn1632Lysfs*14)

PMID: 30204727

Gene: ABCA4

HGNC ID: 34

PMID: 37628710

Gene: ABCA4

HGNC ID: 34

PMID:39967245

Gene: ABCA4

HGNC ID: 34

Case#:39 man

DiseaseAssertion:NA

FamilyInfo:NA

CasePresentingHPOs:Snellen in both eye, visual impairment with night blindnessisual acuity was 20/20Snellen in both eyes, with a minor correction for astig-matism. The anterior segment and intraocular pressurewere within normal limits. On fundus examination, dif-fuse fleck-like lesions were scattered both inside and out-side the arcades, while sharply demarcated areas ofmacular atrophy with foveal sparing, more pronouncedin the left eye, were visible.

CaseHPOFreeText:NA

CaseNotHPOs:NA

CaseNotHPOFreeText:

Genotyping Method:Next-Generation Sequencing (NGS), using theTruSight One Clinical Exome sequencing panel on anIllumina NexSeq500 platform, enriching for 4800 genesincluding ABCA4, CNGB3, ELOVL4, PROM1, and PRPH2

PreviouslyPublished:Under refernces?

Variant:WDR19 variants:the novel deletion at c.1777 + 1 within the donor splicingsite (class 4) and the rare c.1430 G>T variant causing theamino-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 throughSanger sequencing

ClinVar:NA

CAID:NA

SupplementalData:NA

PMID:39215425

Gene: ABCA4

HGNC ID: 34

case27-year-old male, the brother of case 1

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: Case 2, a 27-year-old male, the brother of case 1 had blurry vision which was not corrected with an eyeglass and inconveniences under bright light starting from 14 years ago. Case 2 also underwent a fundus examination after finding that case 1 was RP. In further examination of those patients and their family members found that case 1 was confirmed as RP and case 2

CaseHPOFreeText:NA

CaseNotHPOs:NA

CaseNotHPOFreeText:NA

Genotyping Method:NA

PreviouslyPublished:NA

Variant:NA

ClinVar:

CAID:NA

SupplementalData:NA

Inheritance pattern Autosomal Recessive