Neurological ciliopathies

Gene: LRRC45

Green List (high evidence)

Comment on list classification: There are 5 individuals from 4 unrelated families reported in literature with biallelic variants in LRRC45. The individuals presented with a range of symptoms from the ciliopathy spectrum: severe neurodevelopmental delay, seizures, cone-rod dystrophy, respiratory insufficiency, muscular hypotonia. The c.1402-2A>G variant was shown to result in a significant reduction of primary cilia frequency and length in patient fibroblasts. In addition, LRRC45 is known to have a role in ciliogenesis. Based on the available evidence, LRRC45 should be promoted to Green for Neurological ciliopathies at the next GMS update.

Created: 11 Nov 2025, 11:47 a.m. | Last Modified: 11 Nov 2025, 11:47 a.m.

Panel Version: 6.11

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

Created: 11 Nov 2025, 11:30 a.m. | Last Modified: 11 Nov 2025, 11:53 a.m.

Panel Version: 6.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
ciliopathy, MONDO:0005308; Abnormal brain morphology, HP:0012443; neurodevelopmental disorder, MONDO:0700092

Publications

• 30131441
• 34716235
• 39638757