Activity
| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
5 actions
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ophthalmological ciliopathies v5.9 | LRRC45 | Ida Ertmanska changed review comment from: Comment on list classification: There are 5 individuals from 4 unrelated families with biallelic variants in LRRC45. 2/5 individuals were noted to have an ophthalmological phenotype: isolated cone-rod dystrophy, and nystagmus as part of a syndromic presentation (PMIDs: 34716235; 39638757). Another individual was diagnosed with Bardet-Biedl syndrome-like multi-systemic ciliopathy - often associated with ocular findings, though not specified in the report (PMID: 34716235).; to: Comment on list classification: There are 5 individuals from 4 unrelated families with biallelic variants in LRRC45. 2/5 individuals were noted to have an ophthalmological phenotype: isolated cone-rod dystrophy, and nystagmus as part of a syndromic presentation (PMIDs: 34716235; 39638757). Another individual was diagnosed with Bardet-Biedl syndrome-like multi-systemic ciliopathy - often associated with ocular findings, though not specified in the report (PMID: 34716235). Based on the available evidence, this gene should be rated Amber for Ophthalmological ciliopathies until more evidence emerges. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ophthalmological ciliopathies v5.9 | LRRC45 | Ida Ertmanska commented on gene: LRRC45: Comment on list classification: There are 5 individuals from 4 unrelated families with biallelic variants in LRRC45. 2/5 individuals were noted to have an ophthalmological phenotype: isolated cone-rod dystrophy, and nystagmus as part of a syndromic presentation (PMIDs: 34716235; 39638757). Another individual was diagnosed with Bardet-Biedl syndrome-like multi-systemic ciliopathy - often associated with ocular findings, though not specified in the report (PMID: 34716235). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ophthalmological ciliopathies v5.9 | LRRC45 | Ida Ertmanska Classified gene: LRRC45 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ophthalmological ciliopathies v5.9 | LRRC45 | Ida Ertmanska Gene: lrrc45 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ophthalmological ciliopathies v5.8 | LRRC45 |
Ida Ertmanska gene: LRRC45 was added gene: LRRC45 was added to Ophthalmological ciliopathies. Sources: Literature Mode of inheritance for gene: LRRC45 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: LRRC45 were set to 30131441; 34716235; 39638757 Phenotypes for gene: LRRC45 were set to ciliopathy, MONDO:0005308; Abnormal brain morphology, HP:0012443; neurodevelopmental disorder, MONDO:0700092 Review for gene: LRRC45 was set to AMBER Added comment: PMID: 34716235 Best et al., 2022 2 unrelated individuals with LP biallelic variants in LRRC45. Proband 1 (CMC Patient 48): Bardet-Biedl syndrome-like multi-systemic ciliopathy - homozygous for NM_144999.4: c.1074_1075insTG, p.(Leu359CysfsTer19), also homozygous for CFAP45 (CCDC19) NM_012337.3: c.433C>T, p.(Arg145Ter). Sibling with developmental delay and ID was homozygous for the LRRC45 variant, did not harbour the CFAP45 mutation (proposed to account for the ciliopathy phenotype); parents confirmed as het for each. Proband 2: presented with cone-rod dystrophy (possible ciliopathy basis) - compound het: NM_144999.4: c.1A>T, p.Met1? & NM_144999.4: c.1126–1G>A. Singleton case. PMID: 39638757 Radhakrishnan et al., 2025 Report of 3 individuals from 2 unrelated families with severe central nervous system anomalies, harbouring biallelic variants in LRRC45: P1: c.1402-2A>G; P2 and P3: c.1262G>C (p.Arg421Thr). Method: Exome seq. P1 - female, onset at 1yr 8months, Indian origin, presented with febrile seizures and developmental delay, severe brain anomalies. At 3yr 7 mo: titubation, nystagmus, axial and peripheral hypotonia, normal deep tendon reflexes and pes planus. P2 & 3 - born to Turkish consanguineous parents; P2 - female, presented with severe muscular hypotonia, respiratory insufficiency, and apnea bradycardia syndrome; ophthalmological exam was normal; patient died at 3 months old. P3 - male fetus, pregnancy terminated. Functional evidence - P1 fibroblasts - variant c.1402-2A>G shown to result in a transcript lacking exon 14 (total 17 exons); LRRC45 mRNA and protein levels significantly reduced; significant reduction of primary cilia frequency and length. c.1402-2A>G - splice acceptor - MAF 0.0001647 (South Asian population, 14 heterozygotes - gnomAD v4.1). c.1262G>C (p.Arg421Thr) - MAF 8.475e-7 (1 het in European pop - gnomAD v4.1); Revel score = Uncertain (0.31). Functional evidence: PMID: 30131441 Kurtulmus et al., 2018 - LRRC45 shown to be associated with the basal body of primary and motile cilia in both differentiated and stem cells - broad function in ciliogenesis. This gene is not yet associated with a disease in OMIM (accessed 11th Nov 2025). Sources: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||