A rare genetic variant has been identified in a father and his two daughters, all of whom developed different but serious psychiatric and neurodevelopmental conditions. The findings, published in the Indian Journal of Psychological Medicine, sheds new light on how a single gene mutation can produce a wide range of mental health symptoms across generations.
The gene in question is MYT1L, a transcription factor involved in the development of the nervous system. Mutations in this gene have previously been linked to intellectual disability, autism spectrum disorder, obesity, and in some cases schizophrenia. What makes this case unusual is that the same novel variant was shared by three individuals in one family, yet each presented with markedly different clinical features.
The father, a 50-year-old man, had experienced repeated episodes of psychosis, aggression, and overvalued ideas over more than a decade. He also developed severe movement-related side effects from antipsychotic treatment, including features of parkinsonism and tardive dyskinesia. His cognitive testing later revealed scores significantly below the normal range.
His elder daughter, aged 22, had struggled since childhood with poor academic performance, limited social interaction, and difficulties with daily tasks. When she was eventually treated with antipsychotics, she developed what clinicians suspected was neuroleptic malignant syndrome, a rare but life-threatening reaction to psychiatric drugs. Her condition was further complicated by mood instability and auditory hallucinations.
The younger daughter, aged 17, presented quite differently. She developed severe depression, nihilistic thinking, and catatonia, a condition characterised by unresponsiveness, rigidity, and withdrawal. She responded to electroconvulsive therapy and was eventually stabilised on a combination of mood-stabilising and antidepressant drugs.
All three individuals underwent whole-exome sequencing, which identified a variant labelled c.2612A>C in the MYT1L gene. This specific mutation had not been previously documented in the scientific literature, making it a novel finding. The mutation is predicted to alter the structural properties of the protein the gene produces, potentially disrupting normal brain development.
Researchers noted that the MYT1L protein interacts with DISC1, a gene already known to be a risk factor for both intellectual disability and conditions such as schizophrenia and bipolar disorder. This interaction may help explain why disruptions to MYT1L can produce such varied neuropsychiatric presentations across individuals who carry the same mutation.
The case adds to a growing body of research suggesting that rare inherited gene mutations play a more significant role in psychiatric conditions than previously appreciated. It also raises important questions about genetic testing for families where multiple members experience serious mental illness or neurodevelopmental difficulties.
Clinicians are increasingly being urged to consider genetic factors when patients show unusual sensitivity to antipsychotic drugs or when psychiatric illness clusters across generations within a family. Early genetic screening in such cases could help guide safer and more targeted treatment decisions.