A duplication on chromosome 16q12 affecting the IRXB gene cluster is associated with autosomal dominant cone dystrophy with early tritanopic color vision defect. Issue 13 (22nd April 2021)

• Record Type: Journal Article
• Authors: Kohl, Susanne; Llavona, Pablo; Sauer, Alexandra; Reuter, Peggy; Weisschuh, Nicole; Kempf, Melanie; Dehmelt, Florian Alexander; Arrenberg, Aristides B; Sliesoraityte, Ieva; Zrenner, Eberhart; van Schooneveld, Mary J; Rudolph, Günther; Kühlewein, Laura; Wissinger, Bernd
• Is Part Of: Human molecular genetics. Volume 30:Issue 13(2021)
• Page Start: 1218
• Page End: 1229
• Publication Date: 2021-04-22
• Subjects: Human molecular genetics -- Periodicals; Human chromosome abnormalities -- Periodicals; 572.8
• DOI: 10.1093/hmg/ddab117
• Languages: English
• ISSNs: 0964-6906

Abstract

Abstract: Cone dystrophies are a rare subgroup of inherited retinal dystrophies and hallmarked by color vision defects, low or decreasing visual acuity and central vision loss, nystagmus and photophobia. Applying genome-wide linkage analysis and array comparative genome hybridization, we identified a locus for autosomal dominant cone dystrophy on chromosome 16q12 in four independent multigeneration families. The locus is defined by duplications of variable size with a smallest region of overlap of 608 kb affecting the IRXB gene cluster and encompasses the genes IRX5 and IRX6 . IRX5 and IRX6 belong to the Iroquois (Iro) protein family of homeodomain-containing transcription factors involved in patterning and regionalization of embryonic tissue in vertebrates, including the eye and the retina. All patients presented with a unique progressive cone dystrophy phenotype hallmarked by early tritanopic color vision defects. We propose that the disease underlies a misregulation of the IRXB gene cluster on chromosome 16q12 and demonstrate that overexpression of Irx5a and Irx6a, the two orthologous genes in zebrafish, results in visual impairment in 5-day-old zebrafish larvae.