Unravelling genotype-phenotype correlations in Stargardt disease using patient-derived retinal organoids.

• Tác giả: Lyle Armstrong, Robert Atkinson, Valeria Chichagova, Joseph Collin, Ana Conesa, Jonathan Coxhead, Frans P M Cremers, Birthe Dorgau, Luis Ferrández-Peral, Rafiqul Hussain, Majlinda Lako, Michael McCorkindale, Andrew Nelson, Rachel Queen, Avril Watson, Darin Zerti
• Ngôn ngữ: eng
• Ký hiệu phân loại: 025.3177 Bibliographic analysis and control
• Thông tin xuất bản: England : Cell death & disease , 2025
• Bộ sưu tập: NCBI
• ID: 469307

Tóm tắt

 Stargardt disease is an inherited retinopathy affecting approximately 1:8000 individuals. It is characterised by biallelic variants in ABCA4 which encodes a vital protein for the recycling of retinaldehydes in the retina. Despite its prevalence and impact, there are currently no treatments available for this condition. Furthermore, 35% of STGD1 cases remain genetically unsolved. To investigate the cellular and molecular characteristics associated with STGD1, we generated iPSCs from two monoallelic unresolved (PT1 & PT2), late-onset STGD1 cases with the heterozygous complex allele - c.[5461-10 T >
  C
 5603 A >
  T]. Both patient iPSCs and those from a biallelic affected control (AC) carrying -c.4892 T >
  C and c.4539+2001G >
  A, were differentiated to retinal organoids, which developed all key retinal neurons and photoreceptors with outer segments positive for ABCA4 expression. We observed patient-specific disruption to lamination with OPN1MW/LW