Clinical and Laboratory ObservationsLethal Disorder of Mitochondrial Fission Caused by Mutations in DNM1L
Section snippets
Methods
This study was approved by the Research Ethics Board of the Hospital for Sick Children and written consent was obtained from the family to participate in this study.
Patient A, a female, was born to a 37-year-old gravida 2 para 0 abortions 1 mother after 12 years of infertility. Parents were non-consanguineous and of Filipino background. Pregnancy was complicated by twin gestation with fetal death of the second twin at 21 weeks. Patient A was delivered by cesarean at 36 weeks for non-reassuring
Results
Both infants had detailed neuropathologic evaluation at autopsy and were found to have similar abnormalities (Figure 1). Many neurons in the brain and spinal cord contained intracytoplasmic hyaline eosinophilic globules. These globules were round, varied in size up to approximately 3 μm, and did not polarize. They were widespread and seen in neurons in all areas of the brain and spinal cord. Hyaline globules were not identified in glial or non-neuronal cells and were not associated with
Discussion
DNM1L is essential for normal embryonic development, and animal models of complete DNM1L deficiency have demonstrated absence of DNM1L is not compatible with life.7, 8 Neurons are particularly vulnerable to DNM1L dysfunction9 and DNM1L (Drp1) knock-out mice had smaller forebrains and marked hypoplasia of the white matter, in addition to giant mitochondria in neurons of the basal ganglia.7 Cerebellar development was defective in the knock-out mice, with Purkinje cells having abnormally shaped
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Cited by (0)
Funded by the Government of Canada through Genome Canada, the Canadian Institutes of Health Research, the Ontario Genomics Institute (OGI-049), Genome Quebec, Genome British Columbia, and the McLaughlin Center. S.S. serves as a paid scientific advisory board member of Population Diagnostics and Younique Genomics; receives royalty fees from Lineagen and Athena; serves on the scientific advisory board of Autism Speaks; and receives funding from GlaxoSmithKline. The other authors declare no conflicts of interest.
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List of additional members of the FORGE Canada Consortium Steering Committee is available at www.jpeds.com (Appendix).