Skip to content
WhatIsLCA
Back to All Types
LCA8

CRB1

Crumbs homolog 1 (CRB1); a transmembrane protein essential for retinal development, apical-basal cell polarity, external limiting membrane (ELM) integrity, and photoreceptor-Müller glia interactions. Part of the Crumbs protein complex (CRB1/CRB2/PALS1/PATJ).

Active Clinical Trials

CRB1 gene therapy is technically challenging due to large cDNA (~4.2 kb exceeding AAV capacity). Leading strategy: AAV-CRB2 gene augmentation (Pellissier 2015, Boon 2023). Preclinical success in mouse models and human retinal organoids. CRISPR base/prime editing also being explored (da Costa 2023). Clinical trial NCT05739643 registered.

Chromosomal Locus

1q31.3

Inheritance

Autosomal Recessive

Frequency

~10% of LCA cases

OMIM #613835

Key Clinical Features

  • 1Thickened, dysplastic retinal appearance with disorganized lamination on OCT
  • 2Nummular pigmentation
  • 3Intraretinal cysts / cystoid macular edema
  • 4Relative preservation of para-arteriolar RPE (PPRPE)
  • 5Highly variable clinical presentation — can cause LCA, RP, RP with Coats-like vasculopathy, or macular dystrophy
  • 6CRB1 coding sequence (~4.2 kb) exceeds AAV packaging capacity — gene therapy uses CRB2 augmentation strategy instead of direct CRB1 replacement
  • 7First identified in 1999 (den Hollander et al.) as RP12 gene; linked to LCA in 2001

Clinical Trials

CRB1 Gene Transfer for Retinal Dystrophy

Academic · Phase 1/2

Listed
ClinicalTrials.gov: NCT05739643

Sources: