{
  "abstract": "Background Autosomal dominant (AD) inheritance often arises through haploinsufficiency, dominant-negative or gain of function (GoF) effects, while autosomal recessive (AR) inheritance generally results from partial or complete loss of function (LoF). Yet, a subset of genes demonstrates both inheritance patterns. We aimed to curate a list of such ‘AD/AR’ genes and to propose additional candidates.Methods AD/AR genes were subcategorised based on genotype-phenotype correlations and disease mechanisms. Using bioinformatic analyses, we compared genes with AD, AR and AD/AR inheritance across various metrics, including gnomAD constraint values, exon count, protein length, quaternary structure and gene ontology terms. A machine learning-based metric was used to account for interdependence among features.Results Pathogenic variants in AD/AR genes can lead to distinct or similar phenotypes, depending on the molecular mechanism. AD/AR genes exhibit unique bioinformatic properties such as intermediate constraint scores, a combination of gene ontology terms, a greater average number of exons and an elevated propensity to form homomeric/heteromeric proteins. We identified homozygous LoF or clinically reported variants in nine genes previously classified as AD only.Conclusion Collectively, the data suggest that AD/AR genes possess distinctive features that likely underpin their dual inheritance modes. We propose nine candidate AD/AR genes and emphasise caution in filtering by inheritance type alone.",
  "authors": [
    {
      "affiliations": [
        "Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel",
        "Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"
      ],
      "name": "Shlomit Ezer"
    },
    {
      "affiliations": [
        "Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel",
        "Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"
      ],
      "name": "Tal Sido"
    },
    {
      "affiliations": [
        "Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel",
        "Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"
      ],
      "name": "Jonathan Rips"
    },
    {
      "affiliations": [
        "Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel",
        "Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"
      ],
      "name": "Ronit Hoffman Lipschuetz"
    },
    {
      "affiliations": [
        "Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel",
        "Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"
      ],
      "name": "Adina Fuchs"
    },
    {
      "affiliations": [
        "Department of Pediatrics & Genetics, Makassed Hospital & Al-Quds Medical School, East Jerusalem, Palestine"
      ],
      "name": "Bassam Abu-Libdeh"
    },
    {
      "affiliations": [
        "The Genetics Institute and Center of Rare Diseases, Emek Medical Center, Afula, Israel",
        "Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel"
      ],
      "name": "Elena Chervinsky"
    },
    {
      "affiliations": [
        "Department of Pediatrics & Genetics, Makassed Hospital & Al-Quds Medical School, East Jerusalem, Palestine"
      ],
      "name": "Nadirah S Damseh"
    },
    {
      "affiliations": [
        "The Genetics Institute and Center of Rare Diseases, Emek Medical Center, Afula, Israel"
      ],
      "name": "Nada Danial-Farran"
    },
    {
      "affiliations": [
        "Department of Genetics, Ziv Medical Center, Safed, Israel"
      ],
      "name": "Ilham Morani"
    },
    {
      "affiliations": [
        "Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel",
        "Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"
      ],
      "name": "Ann Saada"
    },
    {
      "affiliations": [
        "INNOVIA Genetic Health Center, INNOVIA Biobank, Amman, Jordan"
      ],
      "name": "Mohammed Al-Raqad"
    },
    {
      "affiliations": [
        "Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel",
        "Genetic Unit, Palestine Red Crescent Society Hospital, Hebron, Palestine"
      ],
      "name": "Somaya Salah"
    },
    {
      "affiliations": [
        "Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel"
      ],
      "name": "Shira Yanovsky-Dagan"
    },
    {
      "affiliations": [
        "Department of Genetics, Ziv Medical Center, Safed, Israel",
        "Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel"
      ],
      "name": "Nadra Samra"
    },
    {
      "affiliations": [
        "Department of Genetics and Metabolic Disorders, Ziv Medical Center, Safed, Israel"
      ],
      "name": "Hanna Mandel"
    },
    {
      "affiliations": [
        "The Genetics Institute and Center of Rare Diseases, Emek Medical Center, Afula, Israel",
        "Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel"
      ],
      "name": "Stavit A Shalev"
    },
    {
      "affiliations": [
        "Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel",
        "Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"
      ],
      "name": "Hagar Mor-Shaked"
    },
    {
      "affiliations": [
        "Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"
      ],
      "name": "Joël Zlotogora"
    },
    {
      "affiliations": [
        "Department of Genetics, Hadassah Medical Organization, Jerusalem, Israel",
        "Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel"
      ],
      "name": "Tamar Harel"
    }
  ],
  "title": "Exploring the unique characteristics of genes with dual autosomal dominant and recessive inheritance: mechanisms, phenotypes and candidate identification",
  "uid": "beb88e5b-466f-541b-a0ec-f4f4e0b94c6e"
}