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| Structural eye disease v4.27 | NTN1 |
Ida Ertmanska changed review comment from: As reviewed by Hannah Knight, PMID: 39648562 (Toms et al., 2024) reports a patient with chorioretinal coloboma and microphthalmia, heterozygous for NM_004822.3:c.1483T>A p.(Tyr495Asn). The patient (Female, 30 years old, White British) also had bilateral sensorineural hearing loss and right hand polydactyly. The C-terminus variant is not found in gnomAD v4.1.0; in silico prediction tools: Revel score = 0.5 (Uncertain), AlphaMissense score = 0.806 (Deleterious Supporting); predicted NMD escape (https://www.deciphergenomics.org/gene/NTN1/overview/protein-genomic-info). Confoundingly, patients with congenital mirror movements from 3 families reported in PMID: 28945198 (Meneret et al., 2017) who also harboured heterozygous NTN1 variants at the C-terminal end (p.Cys601Arg, p.Ile518del, p.Cys601Ser) had normal eyesight, no oculomotor abnormalities, and no hearing impairment. Mouse, chick, and zebrafish models provide good evidence for NTN1's function in optic fissure fusion: In PMID: 39648562, morpholino knockdown of ntn1a in zebrafish (86% gene similarity to human ortholog) had ocular coloboma and sensory hair cell defects. PMID: 31162046 (Hardy et al.,2019): Gene knockdown in zebrafish, using sgRNA targeting the first exon of ntn1. Homozygous knockouts were phenotypic; meanwhile heterozygous fish had no ocular abnormalities. Ntn1-/- mice also displayed highly penetrant ocular coloboma (10/11). Transcriptomic profiling in chick embryos showed that NTN1 is expressed in the chick optic fissure closure. This gene appears to be intolerant to LoF variants (NTN1 pLI score = 1). NTN1 is associated with Mirror movements 4, OMIM:618264 (OMIM entry accessed 10th Sep 2025). Based on the available evidence, this gene can only be rated Amber for Structural eye disease.; to: As reviewed by Hannah Knight, PMID: 39648562 (Toms et al., 2024) reports a patient with chorioretinal coloboma and microphthalmia, heterozygous for a de novo variant in NTN1: NM_004822.3:c.1483T>A p.(Tyr495Asn). Sequencing method: WGS.The patient (Female, 30 years old, White British) also had bilateral sensorineural hearing loss and right hand polydactyly. The C-terminus variant is not found in gnomAD v4.1.0; in silico prediction tools: Revel score = 0.5 (Uncertain), AlphaMissense score = 0.806 (Deleterious Supporting); predicted NMD escape (https://www.deciphergenomics.org/gene/NTN1/overview/protein-genomic-info). Confoundingly, patients with congenital mirror movements from 3 families reported in PMID: 28945198 (Meneret et al., 2017) who also harboured heterozygous NTN1 variants at the C-terminal end (p.Cys601Arg, p.Ile518del, p.Cys601Ser) had normal eyesight, no oculomotor abnormalities, and no hearing impairment. Mouse, chick, and zebrafish models provide good evidence for NTN1's function in optic fissure fusion: In PMID: 39648562, morpholino knockdown of ntn1a in zebrafish (86% gene similarity to human ortholog) had ocular coloboma and sensory hair cell defects. PMID: 31162046 (Hardy et al.,2019): Gene knockdown in zebrafish, using sgRNA targeting the first exon of ntn1. Homozygous knockouts were phenotypic; meanwhile heterozygous fish had no ocular abnormalities. Ntn1-/- mice also displayed highly penetrant ocular coloboma (10/11). Transcriptomic profiling in chick embryos showed that NTN1 is expressed in the chick optic fissure closure. This gene appears to be intolerant to LoF variants (NTN1 pLI score = 1). NTN1 is associated with Mirror movements 4, OMIM:618264 (OMIM entry accessed 10th Sep 2025). Based on the available evidence, this gene can only be rated Amber for Structural eye disease. |
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| Structural eye disease v4.18 | NTN1 |
Hannah Knight gene: NTN1 was added gene: NTN1 was added to Structural eye disease. Sources: Literature Mode of inheritance for gene: NTN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NTN1 were set to PMID: 39648562 Phenotypes for gene: NTN1 were set to Chorioretinal Coloboma; Sensorineural Hearing Loss; Polydactyly Review for gene: NTN1 was set to AMBER Added comment: PMID: 39648562 reported a patient with chorioretinal coloboma and microphthalmia who carried a heterozygous NTN1 variant, c.1483T>A p.(Tyr495Asn). Patient also had bilateral sensorineural hearing loss which was investigated by examining the sensory hair cells of ntn1a morphant zebrafish, suggesting a role for netrin‐1 in hair cell development. NTN1 was previously identified as a mediator of optic fissure closure from transcriptome analyses of chick and zebrafish and was shown to cause ocular coloboma when knocked out in both mouse and zebrafish. Sources: Literature |
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| Structural eye disease v1.151 | TYR | Arina Puzriakova Phenotypes for gene: TYR were changed from [Skin/hair/eye pigmentation 3, blue/green eyes]; Albinism, oculocutaneous, type IB, 606952; Eye Disorders; Waardenburg syndrome/albinism, digenic, 103470; [Skin/hair/eye pigmentation 3, light/dark/freckling skin], 601800; Albinism, oculocutaneous, type IA, 203100; {Melanoma, cutaneous malignant, susceptibility to, 8} to Albinism, oculocutaneous, type IA, OMIM:203100; Albinism, oculocutaneous, type IB, OMIM:606952; Waardenburg syndrome/albinism, digenic, OMIM:103470 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v1.150 | TYR | Arina Puzriakova Mode of inheritance for gene: TYR was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.76 | TYRP1 | Nicola Ragge reviewed gene: TYRP1: Rating: RED; Mode of pathogenicity: ; Publications: 10644000; Phenotypes: Albinism, oculocutaneous, type III, [Skin/hair/eye pigmentation, variation in, 11 (Melanesian blond hair)], 203290, 612271; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.76 | TYR | Nicola Ragge reviewed gene: TYR: Rating: RED; Mode of pathogenicity: ; Publications: 28778995; Phenotypes: Albinism, oculocutaneous, type IA, Albinism, oculocutaneous, type IB, Waardenburg syndrome/albinism, digenic, [Skin/hair/eye pigmentation 3, blue/green eyes], [Skin/hair/eye pigmentation 3, light/dark/freckling skin], {Melanoma, cutaneous malignant, susceptibility to, 8}, 203100, 606952, 103470, 601800, 601800, 601800; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.48 | TYRP1 | Ivone Leong edited their review of gene: TYRP1: Changed phenotypes: Albinism, oculocutaneous, type III, 203290, [Skin/hair/eye pigmentation, variation in, 11 (Melanesian blond hair)], 612271 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.48 | TYR | Ivone Leong edited their review of gene: TYR: Changed phenotypes: Albinism, oculocutaneous, type IA, 203100, Albinism, oculocutaneous, type IB, 606952, Waardenburg syndrome/albinism, digenic, 103470, [Skin/hair/eye pigmentation 3, blue/green eyes], [Skin/hair/eye pigmentation 3, light/dark/freckling skin], 601800, {Melanoma, cutaneous malignant, susceptibility to, 8} | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.38 | TYRP1 | Ivone Leong reviewed gene: TYRP1: Rating: RED; Mode of pathogenicity: ; Publications: 10644000; Phenotypes: Cone-rod dystrophy, Immunodeficiency 13, 615518; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.38 | TYR | Ivone Leong reviewed gene: TYR: Rating: RED; Mode of pathogenicity: ; Publications: 28778995; Phenotypes: Albinism, oculocutaneous, type III, 203290, [Skin/hair/eye pigmentation, variation in, 11 (Melanesian blond hair)], 612271; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.15 | TYRP1 |
Ivone Leong Source NHS GMS was added to TYRP1. Mode of inheritance for gene TYRP1 was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes [Skin/hair/eye pigmentation, variation in, 11 (Melanesian blond hair)], 612271; Albinism, oculocutaneous, type III, 203290 for gene: TYRP1 Publications for gene TYRP1 were changed from to 10644000 |
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| Structural eye disease v0.15 | TYR |
Ivone Leong Source NHS GMS was added to TYR. Mode of inheritance for gene TYR was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Added phenotypes [Skin/hair/eye pigmentation 3, blue/green eyes]; Albinism, oculocutaneous, type IB, 606952; Waardenburg syndrome/albinism, digenic, 103470; [Skin/hair/eye pigmentation 3, light/dark/freckling skin], 601800; Albinism, oculocutaneous, type IA, 203100; {Melanoma, cutaneous malignant, susceptibility to, 8} for gene: TYR Publications for gene TYR were changed from to 28778995 |
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| Structural eye disease v0.2 | TYRP1 |
Ellen McDonagh gene: TYRP1 was added gene: TYRP1 was added to Structural eye disease. Sources: Expert Review Red Mode of inheritance for gene: TYRP1 was set to Phenotypes for gene: TYRP1 were set to Eye Disorders |
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| Structural eye disease v0.2 | TYR |
Ellen McDonagh gene: TYR was added gene: TYR was added to Structural eye disease. Sources: Expert Review Red Mode of inheritance for gene: TYR was set to Phenotypes for gene: TYR were set to Eye Disorders |
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