{
  "abstract": "RNU4ATAC is a non-coding gene involved in the minor spliceosome, and is mutated in a spectrum of syndromic skeletal disorders with recessive inheritance. Recently, biallelic RNU4ATAC pathogenic variants were detected in five patients presenting a complex syndromic phenotype and a brain malformation resembling the ‘molar tooth sign’ (MTS). This is the hallmark of Joubert syndrome (JS), a neurodevelopmental ciliopathy with multiorgan involvement.We reanalysed exome sequencing (ES) from 53 patients with JS, who lacked coding variants in known JS-associated genes. Four RNU4ATAC variants (n.16G>A, n.51G>A, n.13C>T and n.30G>A) were identified in compound heterozygosity in three probands, accounting for 5.6% of negative cases. All patients displayed the MTS and clinical features overlapping those of JS and RNU4ATAC-related skeletal disorders.These findings expand the phenotypic spectrum of RNU4ATAC-related disorders to include a complex neurological-skeletal ciliopathy phenotype, and highlight the relevance of ES reanalysis to uncover non-coding variants often undetected by conventional diagnostics.",
  "authors": [
    {
      "affiliations": [
        "Neurogenetics Research Centre, IRCCS Mondino Foundation, Pavia, Italy"
      ],
      "name": "Fulvio D’Abrusco"
    },
    {
      "affiliations": [
        "Neurogenetics Research Centre, IRCCS Mondino Foundation, Pavia, Italy"
      ],
      "name": "Simone Gana"
    },
    {
      "affiliations": [
        "Pediatric Neurology Unit, Ospedale dei Bambini Vittore Buzzi, Milano, Italy"
      ],
      "name": "Enrico Alfei"
    },
    {
      "affiliations": [
        "Pediatric Unit, IRCCS University Hospital of Bologna Sant Orsola Polyclinic, Bologna, Italy"
      ],
      "name": "Emanuela Scarano"
    },
    {
      "affiliations": [
        "Unit of Muscular and Neurodegenerative Diseases, IRCCS Bambino Gesù Childrens' Hospital, Rome, Italy"
      ],
      "name": "Francesco Nicita"
    },
    {
      "affiliations": [
        "Unit of Muscular and Neurodegenerative Diseases, IRCCS Bambino Gesù Childrens' Hospital, Rome, Italy"
      ],
      "name": "Enrico Silvio Bertini"
    },
    {
      "affiliations": [
        "Rare Diseases and Medical Genetics Unit, IRCCS Bambino Gesù Childrens' Hospital, Rome, Italy"
      ],
      "name": "Maria Cristina Digilio"
    },
    {
      "affiliations": [
        "Rare Diseases and Medical Genetics Unit, IRCCS Bambino Gesù Childrens' Hospital, Rome, Italy"
      ],
      "name": "Ginevra Zanni"
    },
    {
      "affiliations": [
        "Imaging Department, IRCCS Bambino Gesù Childrens' Hospital, Rome, Italy"
      ],
      "name": "Domenico Barbuti"
    },
    {
      "affiliations": [
        "Pediatric Radiology Unit, Vittore Buzzi Children’s Hospital, Milan, Italy"
      ],
      "name": "Eleonora Carlicchi"
    },
    {
      "affiliations": [
        "Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy",
        "Neuroradiology Department, Foundation National Neurological Institute Casimiro Mondino, Pavia, Italy"
      ],
      "name": "Anna Pichiecchio"
    },
    {
      "affiliations": [
        "Developmental Neurology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy"
      ],
      "name": "Stefano D’Arrigo"
    },
    {
      "affiliations": [
        "Department of Molecular Medicine, University of Pavia, Pavia, Italy"
      ],
      "name": "Valentina Serpieri"
    },
    {
      "affiliations": [
        "Neurogenetics Research Centre, IRCCS Mondino Foundation, Pavia, Italy",
        "Department of Molecular Medicine, University of Pavia, Pavia, Italy"
      ],
      "name": "Enza Maria Valente"
    }
  ],
  "title": "Further evidence of RNU4ATAC variants causing Joubert syndrome with skeletal involvement",
  "uid": "376283f6-069c-5b45-bef0-08c410c81059"
}