@article{01HTY934S0SF4CA361TTWQKKKT,
  abstract     = {{Inherited macular dystrophies (iMDs) are a group of genetic disorders, which affect the central region of the retina. To investigate the genetic basis of iMDs, we used single-molecule Molecular Inversion Probes to sequence 105 maculopathy-associated genes in 1352 patients diagnosed with iMDs. Within this cohort, 39.8% of patients were considered genetically explained by 460 different variants in 49 distinct genes of which 73 were novel variants, with some affecting splicing. The top five most frequent causative genes were ABCA4 (37.2%), PRPH2 (6.7%), CDHR1 (6.1%), PROM1 (4.3%) and RP1L1 (3.1%). Interestingly, variants with incomplete penetrance were revealed in almost one-third of patients considered solved (28.1%), and therefore, a proportion of patients may not be explained solely by the variants reported. This includes eight previously reported variants with incomplete penetrance in addition to CDHR1:c.783G>A and CNGB3:c.1208G>A. Notably, segregation analysis was not routinely performed for variant phasing-a limitation, which may also impact the overall diagnostic yield. The relatively high proportion of probands without any putative causal variant (60.2%) highlights the need to explore variants with incomplete penetrance, the potential modifiers of disease and the genetic overlap between iMDs and age-related macular degeneration. Our results provide valuable insights into the genetic landscape of iMDs and warrant future exploration to determine the involvement of other maculopathy genes.}},
  articleno    = {{367}},
  author       = {{Hitti-Malin, Rebekkah J. and  Panneman, Daan M. and  Corradi, Zelia and  Boonen, Erica G. M. and  Astuti, Galuh and  Dhaenens, Claire-Marie and  Stoehr, Heidi and  Weber, Bernhard H. F. and  Sharon, Dror and  Banin, Eyal and  Karali, Marianthi and  Banfi, Sandro and  Ben-Yosef, Tamar and  Glavac, Damjan and  Farrar, G. Jane and  Ayuso, Carmen and  Liskova, Petra and  Dudakova, Lubica and  Vajter, Marie and  Oldak, Monika and  Szaflik, Jacek P. and  Matynia, Anna and  Gorin, Michael B. and  Kaempjaervi, Kati and  Bauwens, Miriam and De Baere, Elfride and  Hoyng, Carel B. and  Li, Catherina H. Z. and  Klaver, Caroline C. W. and  Inglehearn, Chris F. and  Fujinami, Kaoru and  Rivolta, Carlo and  Allikmets, Rando and  Zernant, Jana and  Lee, Winston and  Podhajcer, Osvaldo L. and  Fakin, Ana and  Sajovic, Jana and  Altalbishi, Alaa and  Valeina, Sandra and  Taurina, Gita and  Vincent, Andrea L. and  Roberts, Lisa and  Ramesar, Raj and  Sartor, Giovanna and  Luppi, Elena and  Downes, Susan M. and  van den Born, L. Ingeborgh and  Mclaren, Terri L. and  De Roach, John N. and  Lamey, Tina M. and  Thompson, Jennifer A. and  Chen, Fred K. and  Tracewska, Anna M. and  Kamakari, Smaragda and  Sallum, Juliana Maria Ferraz and  Bolz, Hanno J. and  Kayserili, Huelya and  Roosing, Susanne and  Cremers, Frans P. M.}},
  issn         = {{2218-273X}},
  journal      = {{BIOMOLECULES}},
  keywords     = {{maculopathies,macula,retinal,inherited,sequencing,penetrance,TRANSFER RNALEU(UUR) GENE,MACULAR DEGENERATION,STARGARDT DISEASE,RETINITIS-PIGMENTOSA,MOLECULAR-GENETICS,CLINICAL-FEATURES,RP1L1 VARIANTS,ABCA4,MUTATION,DYSTROPHY}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{20}},
  title        = {{Towards uncovering the role of incomplete penetrance in maculopathies through sequencing of 105 disease-associated genes}},
  url          = {{http://doi.org/10.3390/biom14030367}},
  volume       = {{14}},
  year         = {{2024}},
}

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