{
  "abstract": "Individuals from a 6-octapeptide repeat insertion (6-OPRI) mutation inherited prion disease kindred, with over 100 affected patients, exhibit severe emotional and behavioural difficulties starting in childhood, distinct from the adult-onset prion dementia (Collinge et al, Brain 1992). The direct effects of the PRNP mutation on brain development versus indirect social influences remain unclear. Thematic analysis of 21 6-OPRI recent carriers identified five symptom dimensions: behavioural disturbances(43%), emotional dysregulation(33%), educational challenges(52%), substance use(33%), and motivational abnormalities(10%). Compared to controls, carriers were significantly more likely to exhibit these symptoms (p < 0.001). A case vignette describes an individual with a severe mental disorder of this type, who was adopted from a young age, suggesting neuropsychiatric symptoms may stem directly from the mutation. Plasma neurofilament light levels, a neurodegeneration marker, differed significantly between asymptomatic carriers and symptomatic patients (p = 0.005). We illustrate how biomarkers and MRI brain can help distinguish the kindred’s premorbid syndrome from features of early dementia. Exome sequencing of three related 6-OPRI carriers confirmed the pathogenic mutation but identified no confounding deleterious variants. These findings support the concept of a premorbid neuropsychiatric syndrome linked to the neurodevelopmental effects of 6-OPRI (and by extension other large insertional mutations of PRNP).l.farakish@nhs.net",
  "authors": [
    {
      "affiliations": [
        "MRC Prion Unit at University College London (UCL), UCL Institute of Prion Disease",
        "NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, UCLH NHS Trust"
      ],
      "name": "Farakish Lily"
    },
    {
      "affiliations": [
        "MRC Prion Unit at University College London (UCL), UCL Institute of Prion Disease",
        "NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, UCLH NHS Trust"
      ],
      "name": "Pauli Lucy"
    },
    {
      "affiliations": [
        "Department of Neuropsychology, National Hospital for Neurology and Neurosurgery, UCLH NHS Trust",
        "Institute of Neurology, University College London (UCL)"
      ],
      "name": "Chan Edgar"
    },
    {
      "affiliations": [
        "MRC Prion Unit at University College London (UCL), UCL Institute of Prion Disease",
        "NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, UCLH NHS Trust"
      ],
      "name": "Mok Tze How"
    },
    {
      "affiliations": [
        "MRC Prion Unit at University College London (UCL), UCL Institute of Prion Disease",
        "NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, UCLH NHS Trust"
      ],
      "name": "Williams Rachel"
    },
    {
      "affiliations": [
        "MRC Prion Unit at University College London (UCL), UCL Institute of Prion Disease"
      ],
      "name": "Darwent Lee"
    },
    {
      "affiliations": [
        "Thornford Park Hospital, Crookham Hill, Crookham Common, Thatcham, Berkshire, RG19 8ET"
      ],
      "name": "Morton David"
    },
    {
      "affiliations": [
        "Thornford Park Hospital, Crookham Hill, Crookham Common, Thatcham, Berkshire, RG19 8ET"
      ],
      "name": "Rusirevi Primrose"
    },
    {
      "affiliations": [
        "MRC Prion Unit at University College London (UCL), UCL Institute of Prion Disease",
        "NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, UCLH NHS Trust"
      ],
      "name": "Collinge John"
    },
    {
      "affiliations": [
        "MRC Prion Unit at University College London (UCL), UCL Institute of Prion Disease",
        "NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery, UCLH NHS Trust"
      ],
      "name": "Mead Simon"
    }
  ],
  "title": "157 Premorbid behavioural, emotional and educational difficulties in 6-octapeptide repeat insertion inherited prion disease",
  "uid": "588ea0fd-ccce-5077-8fec-7259dbb3b34c"
}