Dystrophinopathy with a DMD exon 49–50 deletion in a female patient who developed schizophrenia: An autopsy case

Abstract Background Mutations in DMD affect not only muscles but also the brain. Cases of schizophrenia with DMD mutations have been described previously. Although female dystrophinopathy often has a milder phenotype, some affected females also have intellectual disabilities and psychiatric disorders. We herein present an integrated account of the clinical course, genetic information, and neuropathological findings of a female patient with dystrophinopathy who developed schizophrenia. Case Presentation The patient exhibited a developmental delay, intellectual disability, and schizophrenia, and died at 66 years of age from renal and heart failure. A copy number variation analysis and whole‐genome sequencing revealed a heterozygous deletion in chrX: 31774440–31859356 (hg38), encompassing exons 49 and 50 of DMD (NM₀04006. 3). A neuropathological examination showed that the cortical layers were largely preserved; however, in parts of the visual cortex, some neurons were densely arranged in a line across layers IV–V, and single‐neuronal heterotopias were observed in the subependymal regions around the lateral ventricles and within the white matter of the middle frontal gyrus. These findings suggest focal abnormal brain development that was milder than that reported in Duchenne muscular dystrophy, which may in part reflect the reduced and mosaic expression of dystrophin due to X‐chromosome inactivation. Conclusion The neuropathological findings in this case and in previous studies of Duchenne muscular dystrophy partially overlap with those of schizophrenia. To elucidate the pathogenesis and relationship between schizophrenia and DMD mutations, clinical and research attention should be directed toward the coexistence of both disorders.