{
  "abstract": "Background Inherited retinal diseases (IRDs) are a group of disorders often resulting in progressive vision loss, ultimately leading to blindness. A significant portion of their genetic causes remain unresolved, partly due to undiscovered disease-associated genes or variants. This study aimed to identify novel genetic links to IRDs.Methods All patients underwent comprehensive ophthalmological evaluation, including retinal imaging (fundus autofluorescence and macular optical coherence tomography) and electroretinogram testing. Whole exome sequencing and whole genome sequencing were performed on patients with clinically unsolved IRD, and data were analysed using an in-house pipeline to identify causal variants. Subsequently, Sanger sequencing was performed to confirm identified variants.Results Three unrelated patients from Europe, Middle East and East Asia were identified with unique late-onset retinal degeneration (Stargardt-like phenotype) associated with biallelic loss-of-function (LoF) variants in C19orf44 (HGNC: 26141), a gene of unknown function. The homozygous variant NM_032207.2:c.549_550del;p.Ser185Profs*2 was identified in two unrelated patients (European and Middle Eastern). Moreover, an East Asian patient had likely compound heterozygous LoF variants (NM_032207.2:c.1168C>T;p.Gln390*/c.976_977del;p.Leu326Lysfs*15).Conclusions Our findings establish C19orf44 as a novel disease-causing gene for IRD with Stargardt-like phenotype, expanding the genetic landscape of retinal degeneration.",
  "authors": [
    {
      "affiliations": [
        "Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA"
      ],
      "name": "Hafiz Muhammad Jafar Hussain"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Center for Translational Vision Research, Irvine School of Medicine, University of California, Irvine, California, USA"
      ],
      "name": "Wang Meng"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Center for Translational Vision Research, Irvine School of Medicine, University of California, Irvine, California, USA"
      ],
      "name": "Yumei Li"
    },
    {
      "affiliations": [
        "Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA",
        "Department of Zoology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan"
      ],
      "name": "Sabika Firasat"
    },
    {
      "affiliations": [
        "Retina Foundation of the Southwest, Southwest, Dallas, Texas, USA",
        "Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA"
      ],
      "name": "Mark E Pennesi"
    },
    {
      "affiliations": [
        "Jules Stein Eye Institute, University of California Los Angeles, Los Angeles, California, USA",
        "Department of Ophthalmology, University of California Los Angeles David Geffen School of Medicine, Los Angeles, California, USA"
      ],
      "name": "Michael B Gorin"
    },
    {
      "affiliations": [
        "Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, Maryland, USA"
      ],
      "name": "Bin Guan"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA"
      ],
      "name": "Rebecca Lynn Clark"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA"
      ],
      "name": "Emma Fale-Olsen"
    },
    {
      "affiliations": [
        "Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, Maryland, USA"
      ],
      "name": "Ranya Al Rawi"
    },
    {
      "affiliations": [
        "Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, Maryland, USA"
      ],
      "name": "Aime Agather"
    },
    {
      "affiliations": [
        "Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, Maryland, USA"
      ],
      "name": "Laryssa A Huryn"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA"
      ],
      "name": "Paul Yang"
    },
    {
      "affiliations": [
        "College of Optometry, University of Houston, Houston, Texas, USA"
      ],
      "name": "Anna Matynia"
    },
    {
      "affiliations": [
        "Department of Ophthalmology, Center for Translational Vision Research, Irvine School of Medicine, University of California, Irvine, California, USA"
      ],
      "name": "Rui Chen"
    }
  ],
  "title": "Biallelic loss-of-function variants in C19orf44 lead to retinal degeneration",
  "uid": "77269d5c-f589-5305-bf69-047bd7e9dd79"
}