{
  "abstract": "Biallelic variants in NUP107 cause isolated or syndromic steroid-resistant nephrotic syndrome (SRNS), characterised by proteinuria, hypoalbuminaemia and focal segmental glomerulosclerosis that progresses to end-stage renal disease. Patients with syndromic SRNS have microcephaly, developmental delay or intellectual disability and short stature. Simplified gyration is observed in some individuals. We report on a 2-year-old girl with novel biallelic NUP107 variants, c.2606G>T; p.(Gly869Val) and c.1576+1G>A, proteinuria and a severe neurodevelopmental disorder with microcephaly, developmental delay, early-onset seizures, sensorineural hearing loss and brain structural anomalies, including simplified gyral pattern and hypoplasia of the corpus callosum, pons, brainstem and cerebellum. NUP107 is part of the NUP107-160 complex, which, together with other proteins termed nucleoporins, forms the nuclear pore complex (NPC). The NPC regulates nucleocytoplasmic transport and other cellular processes. In patient-derived fibroblasts, we identified aberrantly spliced NUP107 mRNAs with a frameshift and premature stop codon leading to non-sense-mediated mRNA decay, reduced levels of NUP107 transcripts, reduced NUP107 and NUP133 proteins, and a reduced NPC number. In addition, an abnormal nucleolar morphology was found in patient-derived cells. Our functional data support the conclusion that the NUP107 variants underlie the patient’s phenotype, thereby broadening the clinical spectrum associated with NUP107 variants to include abnormal brain development.",
  "authors": [
    {
      "affiliations": [
        "Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"
      ],
      "name": "Loisa Dana Bonde"
    },
    {
      "affiliations": [
        "Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany",
        "Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany",
        "German Center for Child and Adolescent Health (DZKJ), partner site Hamburg, Hamburg, Germany"
      ],
      "name": "Laura Hecher"
    },
    {
      "affiliations": [
        "Bioinformatics Core, University Medical Center Hamburg-Eppendorf, Hamburg, Germany"
      ],
      "name": "Malik Alawi"
    },
    {
      "affiliations": [
        "Department of Neuroradiology, Queen Elizabeth University Hospital, Glasgow, Scotland, UK"
      ],
      "name": "Kirsten P Forbes"
    },
    {
      "affiliations": [
        "Paediatric Neurology Department, Royal Hospital for Children, Queen Elizabeth University Hospitals, Glasgow, Scotland, UK",
        "Paediatric Neurosciences Research Group, School of Health and Wellbeing, University of Glasgow, Glasgow, Scotland, UK"
      ],
      "name": "Joseph D Symonds"
    },
    {
      "affiliations": [
        "West of Scotland Clinical Genetics Service, Queen Elizabeth University Hospitals, Glasgow, Scotland, UK"
      ],
      "name": "Mark J Hamilton"
    },
    {
      "affiliations": [
        "Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany",
        "German Center for Child and Adolescent Health (DZKJ), partner site Hamburg, Hamburg, Germany"
      ],
      "name": "Kerstin Kutsche"
    }
  ],
  "title": "Novel biallelic NUP107 variants affect the nuclear pore complex and expand the clinical spectrum to include brain malformations",
  "uid": "0519459a-8a16-5acd-9053-41a872f2557e"
}