{
  "abstract": "Deleterious variants in the BRSK2 gene, which encodes a serine/threonine kinase crucial for neuronal polarisation and brain development, have recently been linked to the pathogenesis of autism spectrum disorder (ASD). However, comprehensive clinical descriptions of individuals with pathogenic BRSK2 variants remain limited, and the molecular and cellular consequences of these mutations are poorly understood. This case report provides a detailed clinical, cognitive and molecular characterisation of a male patient with ASD harbouring a de novo BRSK2 frameshift variant, who developed catatonia, developmental regression and cognitive decline during early adolescence. To assess the functional impact of the variant, induced pluripotent stem cells (iPSCs) and iPSC-derived neural organoids were generated from the patient. Molecular analyses revealed a significant reduction in BRSK2 transcript and protein levels. Sequencing of BRSK2 mRNA showed exclusive expression from the wild-type allele, consistent with degradation of the mutant transcript via nonsense-mediated decay. These findings broaden the mutational and phenotypic spectrum associated with BRSK2-related neurodevelopmental disorders and provide functional evidence supporting the pathogenicity of the identified variant. Furthermore, this report demonstrates the role of BRSK2 in complex neuropsychiatric features—such as catatonia and cognitive deterioration, which remain underreported in the existing literature—and emphasises the importance of longitudinal cognitive and behavioural monitoring in individuals with BRSK2 mutations.",
  "authors": [
    {
      "affiliations": [
        "Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil"
      ],
      "name": "Andrea Laurato Sertié"
    },
    {
      "affiliations": [
        "Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil"
      ],
      "name": "Raphaella Josino"
    },
    {
      "affiliations": [
        "Faculdade Israelita de Ciências da Saúde Albert Einstein, Hospital Israelita Albert Einstein, São Paulo, SP, Brazil"
      ],
      "name": "Vitória Rezende Goll"
    },
    {
      "affiliations": [
        "Centro de Estudos do Genoma Humano e Células-tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil"
      ],
      "name": "Ana Luiza Nunes Goussain Filippo"
    },
    {
      "affiliations": [
        "Centro de Estudos do Genoma Humano e Células-tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil"
      ],
      "name": "Gabriele da Silva Campos"
    },
    {
      "affiliations": [
        "Centro de Estudos do Genoma Humano e Células-tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil"
      ],
      "name": "Francisco do Rego"
    },
    {
      "affiliations": [
        "Secretaria de Saúde do Distrito Federal, Fundação de Apoio do Hospital Universitário de Brasília, Brasília, Brazil"
      ],
      "name": "Ellen de Souza Siqueira"
    },
    {
      "affiliations": [
        "Centro de Estudos do Genoma Humano e Células-tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil"
      ],
      "name": "Najila Farias de Alcântara"
    },
    {
      "affiliations": [
        "Centro de Estudos do Genoma Humano e Células-tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil"
      ],
      "name": "Elaine Cristina Zachi"
    },
    {
      "affiliations": [
        "Centro de Estudos do Genoma Humano e Células-tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil"
      ],
      "name": "Maria Rita Passos-Bueno"
    }
  ],
  "title": "Catatonia and regression in an autism spectrum disorder patient harbouring a BRSK2 frameshift mutation",
  "uid": "3aeaa608-4980-5eb9-8f23-b5478a1800af"
}