{
  "abstract": "Background Variants in the Kinesin-family member 5A ( KIF5A) gene are associated with a range of motor diseases, and a strong correlation between the protein domains (motor, stalk and tail) and the clinical phenotype has been proposed. However, several studies have reported exceptions contributing to a complex genotype–phenotype correlation in recent years. Further studies are needed to improve our knowledge about the prevalence of KIF5A variants and their genotype–phenotype correlation.Methods 390 patients (220 hereditary spastic paraplegia, 80 Charcot-Marie-Tooth disease type 2 and 90 amyotrophic lateral sclerosis) have been selected for next-generation sequencing Clinical Exome.Results Five patients have been found to carry causative variants in the KIF5A gene. Of these, three are familiar cases, and two are sporadic. Segregation analysis was performed on the familiar probands. The five patients with pathogenic variants represent 4% of the studied population, and the clinical and genetic analysis of these five families allowed us to examine different scenarios.Some of these data support the hypothesis of a complex correlation between domains and disease.Conclusion These data confirm the complex genotype–phenotype correlation, both in terms of clinical heterogeneity associated with a specific domain and variability within the members of the same family, but also suggest a strong genotype–phenotype correlation, both intrafamiliar and interfamiliar, produced by a few variants.",
  "authors": [
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy"
      ],
      "name": "Rosangela Ferese"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy",
        "Department of Human Neurosciences, University of Rome La Sapienza, Rome, Italy"
      ],
      "name": "Antonio Suppa"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy"
      ],
      "name": "Rosa Campopiano"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy"
      ],
      "name": "Simona Scala"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy"
      ],
      "name": "Federica Sammarone"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy"
      ],
      "name": "Luana Di Pilla"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy"
      ],
      "name": "Alba Di Pardo"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy"
      ],
      "name": "Maria Antonietta Chiaravalloti"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy"
      ],
      "name": "Anna Maria Griguoli"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy"
      ],
      "name": "Milena Cannella"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy"
      ],
      "name": "Carmelo D’Alessio"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy"
      ],
      "name": "Marianna Storto"
    },
    {
      "affiliations": [
        "Department of Biomolecular Sciences, University of Urbino, Urbino, Italy"
      ],
      "name": "Mirco Fanelli"
    },
    {
      "affiliations": [
        "Department of Human Neurosciences, University of Rome La Sapienza, Rome, Italy"
      ],
      "name": "Alessandro Zampogna"
    },
    {
      "affiliations": [
        "Department of Human Neurosciences, University of Rome La Sapienza, Rome, Italy"
      ],
      "name": "Martina Patera"
    },
    {
      "affiliations": [
        "Department of Human Neurosciences, University of Rome La Sapienza, Rome, Italy"
      ],
      "name": "Maurizio Inghilleri"
    },
    {
      "affiliations": [
        "Department of Human Neurosciences, University of Rome La Sapienza, Rome, Italy"
      ],
      "name": "Marco Ceccanti"
    },
    {
      "affiliations": [
        "Department of Human Neurosciences, University of Rome La Sapienza, Rome, Italy"
      ],
      "name": "Chiara Cambieri"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy"
      ],
      "name": "Fabio Buttari"
    },
    {
      "affiliations": [
        "Genomic Medicine Laboratory-UILDM, Fondazione Santa Lucia Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy"
      ],
      "name": "Cristina Peconi"
    },
    {
      "affiliations": [
        "Genomic Medicine Laboratory-UILDM, Fondazione Santa Lucia Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy",
        "Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy"
      ],
      "name": "Emiliano Giardina"
    },
    {
      "affiliations": [
        "Genomic Medicine Laboratory-UILDM, Fondazione Santa Lucia Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy"
      ],
      "name": "Stefania Zampatti"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy",
        "Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy"
      ],
      "name": "Diego Centonze"
    },
    {
      "affiliations": [
        "IRCCS Neuromed, Pozzilli, Italy",
        "Department of Biomolecular Sciences, University of Urbino, Urbino, Italy"
      ],
      "name": "Stefano Gambardella"
    }
  ],
  "title": "New variants and genotype–phenotype correlation in KIF5A mutation: the contribution of a large Italian cohort",
  "uid": "a21e3fd2-41e1-5da6-911d-a718cd819b78"
}