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| Retinal disorders v8.95 | TEAD1 |
Ida Ertmanska changed review comment from: PMID: 15016762 Fossdal et al., 2004 TEAD1 (c.1261T>C, p.Tyr421His) variant identified as causal for first reported Icelandic pedigree with SCRA. Variant not in gnomAD v4.1.0. PMID: 26091538 Schrauwen et al., 2015 Patient with a de novo TEAD1 variant NM_021961.5:c.618G>A; p.Trp206Ter and Aicardi syndrome (infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae). Variant not reported in gnomAD v4.1.0. PMID: 33864784 Grubisa et al., 2021 Serbian family with Sveinsson's chorioretinal atrophy (affected father and 2 children, diagnosed at 45, 20, and 15 years old). TEAD1 sequencing revealed c.1261T>A, p.Tyr421Asn in TEAD1 - not present in gnomAD v4.1.0. Family first reported in PMID: 15359244. PMID: 40984966 Murati Calderon et al., 2025 Report of a 61-year-old Hispanic female patient with clinical features consistent with Sveinsson chorioretinal atrophy (SCRA), including bilateral peripapillary chorioretinal atrophy and early macular involvement. Heterozygous for TEAD1 variant (c.599C>T; p.Ala200Val) - 29 heterozygotes reported in gnomAD v4.1.0. TEAD1 is linked to AD Sveinsson chorioretinal atrophy 108985 in OMIM (accessed 10th Mar 2026).; to: PMID: 15016762 Fossdal et al., 2004 TEAD1 (c.1261T>C, p.Tyr421His) variant identified as causal for first reported Icelandic pedigree with SCRA. Variant not in gnomAD v4.1.0. PMID: 26091538 Schrauwen et al., 2015 Patient with a de novo TEAD1 variant NM_021961.5:c.618G>A; p.Trp206Ter and Aicardi syndrome (infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae). Variant not reported in gnomAD v4.1.0. PMID: 33864784 Grubisa et al., 2021 Serbian family with Sveinsson's chorioretinal atrophy (affected father and 2 children, diagnosed at 45, 20, and 15 years old). TEAD1 sequencing revealed c.1261T>A, p.Tyr421Asn in TEAD1 - not present in gnomAD v4.1.0. Family first reported in PMID: 15359244. PMID: 40984966 Murati Calderon et al., 2025 Report of a 61-year-old Hispanic female patient with clinical features consistent with Sveinsson chorioretinal atrophy (SCRA), including bilateral peripapillary chorioretinal atrophy and early macular involvement. Heterozygous for TEAD1 variant (c.599C>T; p.Ala200Val) - 29 heterozygotes reported in gnomAD v4.1.0. Used a retinal panel of 330 genes. TEAD1 is linked to AD Sveinsson chorioretinal atrophy 108985 in OMIM (accessed 10th Mar 2026). |
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| Retinal disorders v8.78 | AIPL1 |
Ida Ertmanska changed review comment from: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278*. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. Method: WES in proband, Sanger seq in family members. The same mutation (p.W278X) was found in homozygosity in 5 Italian families and in compound het state with another AIPL1 mutation in 3 other families with recessive LCA (PMID: 21474771). Unlikely to be pathogenic dominant. PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease. Supporting functional evidence: PMID: 33067476 Sacristan-Reviriego et al., 2020 - poses that this deletion has an alternative pathogenicity mechanism: PRD-mediated dominant negative effect causing cone-rod dystrophy PMID: 25274777 Ku et al., 2015 - mouse model where p.A352_P355del human AIPL1 transgene was expressed in an Aipl1 null background. In single transgenic mice, the mutant transgene led to a cone-rod dystrophy phenotype, predominantly leading to a slow and progressive cone degeneration. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141* (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. https://doi.org/10.1007/s13258-016-0467-6 Moghadam, Vallian & Vallian, 2017 Same homozygous AIPL1 p.W278* identified in 3 Iranian individuals with LCA with no known consanguinity - likely Iranian founder variant. PMID: 21900377 Pennesi et al., 2011 Family 1: patient was found to have a homozygous Trp278 stop mutation in AIPL1; family 2: two siblings were compound heterozygous for AIPL1 (Leu17Pro and Lys214Asn). Variants confirmed in trans, het parents and sister unaffected. Sequenced 14 LCA-causing genes. PMID: 15249368 Dharmaraj et al., 2004 Cohort of 303 LCA patients. Identified seventeen homozygotes and 9 compound heterozygotes. The ERG of a parent heterozygote carrier (het for W88X) revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025). AIPL1-related Leber congenital amaurosis (biallelic_autosomal) is ranked Definitive in Gene2Phenotype.; to: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278*. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. Method: WES in proband, Sanger seq in family members. The same mutation (p.W278X) was found in homozygosity in 5 Italian families and in compound het state with another AIPL1 mutation in 3 other families with recessive LCA (PMID: 21474771). Unlikely to be pathogenic dominant. PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease. Supporting functional evidence: PMID: 33067476 Sacristan-Reviriego et al., 2020 - poses that this deletion has an alternative pathogenicity mechanism: PRD-mediated dominant negative effect causing cone-rod dystrophy PMID: 25274777 Ku et al., 2015 - mouse model where p.A352_P355del human AIPL1 transgene was expressed in an Aipl1 null background. In single transgenic mice, the mutant transgene led to a cone-rod dystrophy phenotype, predominantly leading to a slow and progressive cone degeneration. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141* (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. PMID: 21900377 Pennesi et al., 2011 Family 1: patient was found to have a homozygous Trp278 stop mutation in AIPL1; family 2: two siblings were compound heterozygous for AIPL1 (Leu17Pro and Lys214Asn). Variants confirmed in trans, het parents and sister unaffected. Sequenced 14 LCA-causing genes. PMID: 15249368 Dharmaraj et al., 2004 Cohort of 303 LCA patients. Identified seventeen homozygotes and 9 compound heterozygotes. The ERG of a parent heterozygote carrier (het for W88X) revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025). AIPL1-related Leber congenital amaurosis (biallelic_autosomal) is ranked Definitive in Gene2Phenotype. |
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| Retinal disorders v8.78 | AIPL1 |
Ida Ertmanska changed review comment from: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 (no PMID?) 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278*. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease PMID: 21900377 Pennesi et al., 2011 The first patient was found to have a homozygous Trp278 stop mutation in AIPL1, whereas the siblings were each found to have novel heterozygous mutations in AIPL1 (Leu17Pro and Lys214Asn). Sequenced 14 LCA-causing genes. PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141* (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. https://doi.org/10.1007/s13258-016-0467-6 Moghadam, Vallian & Vallian, 2017 Same homozygous AIPL1 p.W278* identified in 3 Iranian individuals with LCA with no known consanguinity - likely Iranian founder variant. PMID: 15249368 Dharmaraj et al., 2004 Cohort of 303 LCA patients. Identified seventeen homozygotes and 9 compound heterozygotes. The ERG of a parent heterozygote carrier (het for W88X) revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025). AIPL1-related Leber congenital amaurosis (biallelic_autosomal) is ranked Definitive in Gene2Phenotype.; to: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278*. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. Method: WES in proband, Sanger seq in family members. The same mutation (p.W278X) was found in homozygosity in 5 Italian families and in compound het state with another AIPL1 mutation in 3 other families with recessive LCA (PMID: 21474771). Unlikely to be pathogenic dominant. PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease. Supporting functional evidence: PMID: 33067476 Sacristan-Reviriego et al., 2020 - poses that this deletion has an alternative pathogenicity mechanism: PRD-mediated dominant negative effect causing cone-rod dystrophy PMID: 25274777 Ku et al., 2015 - mouse model where p.A352_P355del human AIPL1 transgene was expressed in an Aipl1 null background. In single transgenic mice, the mutant transgene led to a cone-rod dystrophy phenotype, predominantly leading to a slow and progressive cone degeneration. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141* (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. https://doi.org/10.1007/s13258-016-0467-6 Moghadam, Vallian & Vallian, 2017 Same homozygous AIPL1 p.W278* identified in 3 Iranian individuals with LCA with no known consanguinity - likely Iranian founder variant. PMID: 21900377 Pennesi et al., 2011 Family 1: patient was found to have a homozygous Trp278 stop mutation in AIPL1; family 2: two siblings were compound heterozygous for AIPL1 (Leu17Pro and Lys214Asn). Variants confirmed in trans, het parents and sister unaffected. Sequenced 14 LCA-causing genes. PMID: 15249368 Dharmaraj et al., 2004 Cohort of 303 LCA patients. Identified seventeen homozygotes and 9 compound heterozygotes. The ERG of a parent heterozygote carrier (het for W88X) revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025). AIPL1-related Leber congenital amaurosis (biallelic_autosomal) is ranked Definitive in Gene2Phenotype. |
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| Retinal disorders v8.78 | AIPL1 |
Ida Ertmanska changed review comment from: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 (no PMID?) 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278*. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141* (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. https://doi.org/10.1007/s13258-016-0467-6 Moghadam, Vallian & Vallian, 2017 Same homozygous AIPL1 p.W278* identified in 3 Iranian individuals with LCA with no known consanguinity - likely Iranian founder variant. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025).; to: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 (no PMID?) 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278*. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease PMID: 21900377 Pennesi et al., 2011 The first patient was found to have a homozygous Trp278 stop mutation in AIPL1, whereas the siblings were each found to have novel heterozygous mutations in AIPL1 (Leu17Pro and Lys214Asn). Sequenced 14 LCA-causing genes. PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141* (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. https://doi.org/10.1007/s13258-016-0467-6 Moghadam, Vallian & Vallian, 2017 Same homozygous AIPL1 p.W278* identified in 3 Iranian individuals with LCA with no known consanguinity - likely Iranian founder variant. PMID: 15249368 Dharmaraj et al., 2004 Cohort of 303 LCA patients. Identified seventeen homozygotes and 9 compound heterozygotes. The ERG of a parent heterozygote carrier (het for W88X) revealed significantly reduced rod function, while ERGs for 6 other carrier parents were normal. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025). AIPL1-related Leber congenital amaurosis (biallelic_autosomal) is ranked Definitive in Gene2Phenotype. |
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| Retinal disorders v8.78 | AIPL1 |
Ida Ertmanska changed review comment from: PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025).; to: Monoallelic cases: https://doi.org/10.1016/j.humgen.2025.201413 Ghavidel et al., 2025 (no PMID?) 1 yo Iranian boy, heterozygous for AIPL1: c.834G>A, p.Trp278*. Consanguineous parents. Diagnosed with Leber's congenital amaurosis at 6 months old. Variant has max AF = 0.0004415 in gnomAD v4 (European pop) with 1 homozygote reported. PMID: 33067476 Sacristan-Reviriego et al., 2020 Mutation NM_014336.5(AIPL1):c.1053_1064del (p.Ala352_Pro355del) has MAF of 0.01129 (Ashkenazi Jewish population) in gnomAD v4.1.0, and 3 total homozygotes reported - too high to cause dominant disease PMID: 10873396 Sohocki, et al., 2000 Identified 11 individuals with biallelic AIPL1 variants, as well as 2 apparently dominant pedigree, with affected individuals heterozygous (AIPL1):c.1053_1064del (p.Ala352_Pro355del). Heterozygous individuals presented with juvenile RP or dominant cone-rod dystrophy. Method: sequenced 6 exons of AIPL1 only. The pedigrees are small, dominant segregation not well established. Biallelic cases: PMID: 38880373 Zhang et al., 2024 Cohort of 51 Chinese patients with Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (EOSRD); identified 28 disease-causing AIPL1 variants - biallelic cases only. Most common variant in the cohort was c.421C>T, p.Gln141* (18 patients homozygous, 6 heterozygous + another LoF variant). PMID: 31576779 Wan et al., 2019 2 sibs with Leber congenital amaurosis, homozygous for AIPL1 p.Gln81* variant. Parents both heterozygous for the variant, unaffected. PMID: 24426771 Li et al., 2014 Report of autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Homozygous AIPL1: c.773G>C (p.Arg258Pro) variant detected in family 61032, and a homozygous AIPL1: c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Heterozygous carriers had no signs of retinitis pigmentosa. https://doi.org/10.1007/s13258-016-0467-6 Moghadam, Vallian & Vallian, 2017 Same homozygous AIPL1 p.W278* identified in 3 Iranian individuals with LCA with no known consanguinity - likely Iranian founder variant. The gene-disease relationship between AIPL1 and autosomal dominant retinal dystrophy has been classified as Disputed in ClinGen (Retina GCEP, April 2025). |
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| Retinal disorders v1.159 | LRP2 | Gavin Arno reviewed gene: LRP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.159 | RP2 | Gavin Arno reviewed gene: RP2: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.137 | LRP2 |
Ivone Leong Source NHS GMS was added to LRP2. Rating Changed from Green List (high evidence) to Green List (high evidence) |
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| Retinal disorders v1.137 | RP2 |
Ivone Leong Source NHS GMS was added to RP2. Rating Changed from Green List (high evidence) to Green List (high evidence) |
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| Retinal disorders v1.127 | LRP2 | Ivone Leong Classified gene: LRP2 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.127 | LRP2 | Ivone Leong Added comment: Comment on list classification: Promoted from red to green. LRP2 is associated with a Donnai-Barrow syndrome in OMIM and Gene2Phenotype. Retinal dystrophy is listed as one of the phenotypes in Gene2Phenotype for this gene. There are also >3 unrelated cases of patients with Donnai-Barrow syndrome. Therefore, there is sufficient evidence to promote this gene to green status. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.127 | LRP2 | Ivone Leong Gene: lrp2 has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.126 | LRP2 | Ivone Leong Publications for gene: LRP2 were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.112 | LRP2 | Ivone Leong Phenotypes for gene: LRP2 were changed from Donnai-Barrow syndrome to Donnai-Barrow syndrome 222448 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders | LRP2 | Louise Daugherty classified LRP2 as red | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders | RP2 | BRIDGE consortium reviewed RP2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders | LRP2 | BRIDGE consortium reviewed LRP2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||