Lethal Disorder of Mitochondrial Fission Caused by Mutations in DNM1L

Grace Yoon; Zeenat Malam; Tara Paton; Christian R Marshall; Ella Hyatt; Zhenya Ivakine; Stephen W Scherer; Kyong-Soon Lee; Cynthia Hawkins; Ronald D Cohn; Finding of Rare Disease Genes (FORGE) in Canada Consortium Steering Committee

doi:10.1016/j.jpeds.2015.12.060

Lethal Disorder of Mitochondrial Fission Caused by Mutations in DNM1L

J Pediatr. 2016 Apr:171:313-6.e1-2. doi: 10.1016/j.jpeds.2015.12.060. Epub 2016 Jan 26.

Collaborators

Finding of Rare Disease Genes (FORGE) in Canada Consortium Steering Committee:
Kym M Boycott, Jan Friedman, Jacques Michaud, Francois Bernier, Michael Brudno, Bridget Fernandez, Bartha Knoppers, Mark Samuels

Affiliations

¹ Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. Electronic address: grace.yoon@utoronto.ca.
² Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.
³ Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada; The Center for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
⁴ Division of Neonatology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
⁵ Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
⁶ Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada.

PMID: 26825290
DOI: 10.1016/j.jpeds.2015.12.060

Abstract

We describe two infants with hypotonia, absent respiratory effort, and giant mitochondria in neurons due to compound heterozygosity for 2 nonsense mutations of DNM1L. DNM1L has a critical role in regulating mitochondrial morphology and function. This observation confirms the central role of mitochondrial fission to normal human development.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Codon, Nonsense
DNA Mutational Analysis
Dynamins
Exome
Family Health
Fatal Outcome
Female
Formins
GTP Phosphohydrolases / deficiency
GTP Phosphohydrolases / genetics*
Heterozygote
Humans
Infant, Newborn
Male
Microfilament Proteins / genetics
Microscopy, Fluorescence
Microtubule-Associated Proteins / deficiency
Microtubule-Associated Proteins / genetics*
Mitochondrial Diseases / genetics*
Mitochondrial Dynamics*
Mitochondrial Proteins / deficiency
Mitochondrial Proteins / genetics*
Mutation*
Pedigree

Substances

Codon, Nonsense
Formins
INF2 protein, human
Microfilament Proteins
Microtubule-Associated Proteins
Mitochondrial Proteins
GTP Phosphohydrolases
DNM1L protein, human
Dynamins

Grants and funding

Canadian Institutes of Health Research/Canada