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| Retinal disorders v9.3 | LOXL3 |
Ida Ertmanska changed review comment from: PMID: 41052910 Sanchez et al., 2026 3 sisters with biallelic LOXL3 variants and Stickler Syndrome. Comp het for c.1735C>T, p.Arg579* and c.956G>A, p.Arg319Gln in LOXL3 - targeted NGS panel. Parents are healthy carriers of one LOXL3 variant each. Shared phenotype: skeletal anomalies in feet and hands, cleft palate, high myopia, bilateral conductive hearing loss (2/3). PMID: 38957076 Klejnotowska et al., 2024 4yo boy with reduced visual acuity 6/30 in both eyes, bilateral vitreous syneresis, foveal hypoplasia and bilateral high myopia (-8.50D). A skeletal survey showed mild spondylo-epi-metaphyseal dysplasia. Normal hearing. WES revealed a homozygous LOXL3 variant c.1448_1449del, p.(Thr483Argfs*13), inherited through paternal UPiD of chromosome 2. PMID: 36917121 Jiang et al., 2023 9 unrelated Chinese patients with LOXL3 variants and early-onset extreme high myopia - main and consistent feature across the cohort. No significant skeletal abnormalities, midface development, palate malformation was observed in these nine patients; auditory assessment normal where available. Authors hypothesise that biallelic missense variants result in Stickler syndrome, while truncating variants yield isolated high myopia - this is not very consistent, though. PMID: 30362103 Chan et al., 2019 Report of a child and his father who had clinical features consistent with Stickler syndrome and found to have a homozygous novel mutation c.1036C>T (p.Arg346Trp) in LOXL3. Clinical features: high myopia, short stature, retinal changes, high-arched palate (son only). No hearing loss. PMID: 25663169 Alzahrani et al., 2015 Saudi family with AR Stickler syndrome. Parents are second cousins. Index patient: 16yo boy with cleft palate, micro/retrognathia, non-progressive myopia (-10.00 D) with chorioretinal lattice degeneration, mild conductive hearing loss. 8yo sister has similar presentation, with myopia of -13.00 D and normal hearing. Both had normal development. Homozygous LOXL3 c.2027G>T, p.Cys676Phe detected in the sibs (exome seq + autozygosity filtering). Functional evidence: PMID: 36610533 Liu et al., 2023 - a mouse model of Stickler syndrome was made by inducing a LOXL3 mutation (c.2027G>A, p.Cys676Tyr) using CRISPR/Cas9. The Loxl3 mutant mice exhibited perinatal death, spinal deformity, cleft palate, skeletal dysplasia and progressive visual degeneration. Sources: Literature; to: PMID: 41052910 Sanchez et al., 2026 3 sisters with biallelic LOXL3 variants and Stickler Syndrome. Comp het for c.1735C>T, p.Arg579* and c.956G>A, p.Arg319Gln in LOXL3 - targeted NGS panel. Parents are healthy carriers of one LOXL3 variant each. Shared phenotype: skeletal anomalies in feet and hands, cleft palate, high myopia, bilateral conductive hearing loss (2/3). PMID: 38957076 Klejnotowska et al., 2024 4yo boy with reduced visual acuity 6/30 in both eyes, bilateral vitreous syneresis, foveal hypoplasia and bilateral high myopia (-8.50D). A skeletal survey showed mild spondylo-epi-metaphyseal dysplasia. Normal hearing. WES revealed a homozygous LOXL3 variant c.1448_1449del, p.(Thr483Argfs*13), inherited through paternal UPiD of chromosome 2. PMID: 36917121 Jiang et al., 2023 9 unrelated Chinese patients with LOXL3 variants and early-onset extreme high myopia - main and consistent feature across the cohort. No significant skeletal abnormalities, midface development, palate malformation was observed in these nine patients; auditory assessment normal where available. Authors hypothesise that biallelic missense variants result in Stickler syndrome, while truncating variants yield isolated high myopia - this is not very consistent, though. PMID: 30362103 Chan et al., 2019 Report of a child and his father who had clinical features consistent with Stickler syndrome and found to have a homozygous novel mutation c.1036C>T (p.Arg346Trp) in LOXL3. Clinical features: high myopia, short stature, retinal changes, high-arched palate (son only). No hearing loss. On fundus examination, the father had myopic fundi and peripheral retinal degeneration - seen at age 40 years. The son, age 11 years, had vitreous degeneration/detachment in both eyes. PMID: 25663169 Alzahrani et al., 2015 Saudi family with AR Stickler syndrome. Parents are second cousins. Index patient: 16yo boy with cleft palate, micro/retrognathia, non-progressive myopia (-10.00 D) with chorioretinal lattice degeneration, mild conductive hearing loss. 8yo sister has similar presentation, with myopia of -13.00 D and normal hearing. Both had normal development. Homozygous LOXL3 c.2027G>T, p.Cys676Phe detected in the sibs (exome seq + autozygosity filtering). Functional evidence: PMID: 36610533 Liu et al., 2023 - a mouse model of Stickler syndrome was made by inducing a LOXL3 mutation (c.2027G>A, p.Cys676Tyr) using CRISPR/Cas9. The Loxl3 mutant mice exhibited perinatal death, spinal deformity, cleft palate, skeletal dysplasia and progressive visual degeneration. Sources: Literature |
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| Retinal disorders v9.2 | LOXL3 |
Ida Ertmanska gene: LOXL3 was added gene: LOXL3 was added to Retinal disorders. Sources: Literature Mode of inheritance for gene: LOXL3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LOXL3 were set to 25663169; 30362103; 36610533; 36917121; 38957076; 41052910 Phenotypes for gene: LOXL3 were set to Myopia 28, autosomal recessive, OMIM:619781; Stickler syndrome, MONDO:0019354 Review for gene: LOXL3 was set to GREEN Added comment: PMID: 41052910 Sanchez et al., 2026 3 sisters with biallelic LOXL3 variants and Stickler Syndrome. Comp het for c.1735C>T, p.Arg579* and c.956G>A, p.Arg319Gln in LOXL3 - targeted NGS panel. Parents are healthy carriers of one LOXL3 variant each. Shared phenotype: skeletal anomalies in feet and hands, cleft palate, high myopia, bilateral conductive hearing loss (2/3). PMID: 38957076 Klejnotowska et al., 2024 4yo boy with reduced visual acuity 6/30 in both eyes, bilateral vitreous syneresis, foveal hypoplasia and bilateral high myopia (-8.50D). A skeletal survey showed mild spondylo-epi-metaphyseal dysplasia. Normal hearing. WES revealed a homozygous LOXL3 variant c.1448_1449del, p.(Thr483Argfs*13), inherited through paternal UPiD of chromosome 2. PMID: 36917121 Jiang et al., 2023 9 unrelated Chinese patients with LOXL3 variants and early-onset extreme high myopia - main and consistent feature across the cohort. No significant skeletal abnormalities, midface development, palate malformation was observed in these nine patients; auditory assessment normal where available. Authors hypothesise that biallelic missense variants result in Stickler syndrome, while truncating variants yield isolated high myopia - this is not very consistent, though. PMID: 30362103 Chan et al., 2019 Report of a child and his father who had clinical features consistent with Stickler syndrome and found to have a homozygous novel mutation c.1036C>T (p.Arg346Trp) in LOXL3. Clinical features: high myopia, short stature, retinal changes, high-arched palate (son only). No hearing loss. PMID: 25663169 Alzahrani et al., 2015 Saudi family with AR Stickler syndrome. Parents are second cousins. Index patient: 16yo boy with cleft palate, micro/retrognathia, non-progressive myopia (-10.00 D) with chorioretinal lattice degeneration, mild conductive hearing loss. 8yo sister has similar presentation, with myopia of -13.00 D and normal hearing. Both had normal development. Homozygous LOXL3 c.2027G>T, p.Cys676Phe detected in the sibs (exome seq + autozygosity filtering). Functional evidence: PMID: 36610533 Liu et al., 2023 - a mouse model of Stickler syndrome was made by inducing a LOXL3 mutation (c.2027G>A, p.Cys676Tyr) using CRISPR/Cas9. The Loxl3 mutant mice exhibited perinatal death, spinal deformity, cleft palate, skeletal dysplasia and progressive visual degeneration. Sources: Literature |
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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 v4.36 | CFAP20 |
Zornitza Stark gene: CFAP20 was added gene: CFAP20 was added to Retinal disorders. Sources: Literature Mode of inheritance for gene: CFAP20 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CFAP20 were set to 36329026 Phenotypes for gene: CFAP20 were set to Retinitis pigmentosa (MONDO:0019200) Review for gene: CFAP20 was set to GREEN Added comment: Describe 8 individuals from 4 independent families with damaging biallelic variants (homozygous or compound heterozygous) in CFAP20 that segregate with retinal dystrophy. All variants cluster to one side of the protein, with two of the residues directly contacting alpha-tubullin. Family 1 - consanguineous set of 3 siblings from Sudan, homozygous for CFAP20 c.305G>A; p.Arg102His (they also had a homozygous variant in DYNC1LI2 however CFAP20 was considered the better candidate. Family 2 - 3 siblings from Spain, 2 with retinal dystrophy, 1 genetically tested and has c.337C>T; p.(Arg113Trp) and c.397delC; p.(Gln133Serfs*5) Family 3 - single affected family member compound het for c.164+1G>A and c.457A>G; p.(Arg153Gly). Family 4 - 3 affected siblings with generalised retinopathy and variable neurological deficits with c.164+1G>A and c.257G>A; p.(Tyr86Cys) For all families, no individuals had signs of polycystic kidney disease; however, not all individuals had kidney imaging. Visual defecit phenotype presented between adolescence and adulthood (17-56 years old). Used HEK293T cell expression studies to demonstrate a statistically significant decline of mutated CFAP20 protein levels (with the exception of p.Arg102His). To test the specific variants, they used the C.elegans orthologues. CFAP20 is a ciliopathy candidate. Demonstrate in zebrafish that cfap20 is required for motile cilia function, and in C. elegans, CFAP-20 maintains the structural integrity of non-motile cilia inner junctions, influencing sensory-dependent signalling and development. Sources: Literature |
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| Retinal disorders v1.160 | TYRP1 | Ivone Leong reviewed gene: TYRP1: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.160 | TYR | Ivone Leong reviewed gene: TYR: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.159 | TYRP1 | Gavin Arno reviewed gene: TYRP1: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.159 | TYR | Gavin Arno reviewed gene: TYR: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.137 | TYRP1 | Ivone Leong Source NHS GMS was added to TYRP1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Retinal disorders v1.137 | TYR | Ivone Leong Source NHS GMS was added to TYR. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||