Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
6 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v1.152 | GRN | Arina Puzriakova Phenotypes for gene: GRN were changed from CEROID LIPOFUSCINOSIS, NEURONAL, 11, 614706; Eye Disorders to Ceroid lipofuscinosis, neuronal, 11, OMIM:614706 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.76 | GRN | Nicola Ragge reviewed gene: GRN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CEROID LIPOFUSCINOSIS, NEURONAL, 11, 614706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.38 | GRN | Ivone Leong reviewed gene: GRN: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: CEROID LIPOFUSCINOSIS, NEURONAL, 11, 614706; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.15 | GRN |
Ivone Leong Source NHS GMS was added to GRN. Mode of inheritance for gene GRN was changed from to BIALLELIC, autosomal or pseudoautosomal Added phenotypes CEROID LIPOFUSCINOSIS, NEURONAL, 11, 614706 for gene: GRN |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Structural eye disease v0.2 | GRN |
Ellen McDonagh gene: GRN was added gene: GRN was added to Structural eye disease. Sources: Expert Review Red Mode of inheritance for gene: GRN was set to Phenotypes for gene: GRN were set to Eye Disorders |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||