Deleterious variants in CRLS1 lead to cardiolipin deficiency and cause an autosomal recessive multi-system mitochondrial disease

Richard G Lee; Shanti Balasubramaniam; Maike Stentenbach; Tom Kralj; Timothy McCubbin; Benjamin Padman; Janine Smith; Lisa G Riley; Archana Priyadarshi; Liuyu Peng; Madison R Nuske; Richard Webster; Ken Peacock; Philip Roberts; Zornitza Stark; Gabrielle Lemire; Yoko A Ito; Kym M Boycott; Michael T Geraghty; Jan Bert Klinken; Sacha Ferdinandusse; Ying Zhou; Rebecca Walsh; Esteban Marcellin; David R Thorburn; Tony Rosciolli; Janice Fletcher; Oliver Rackham; Frederic M Vaz; Gavin E Reid; Aleksandra Filipovska

Journal article

Deleterious variants in CRLS1 lead to cardiolipin deficiency and cause an autosomal recessive multi-system mitochondrial disease

Richard G Lee, Shanti Balasubramaniam, Maike Stentenbach, Tom Kralj, Timothy McCubbin, Benjamin Padman, Janine Smith, Lisa G Riley, Archana Priyadarshi, Liuyu Peng, Madison R Nuske, Richard Webster, Ken Peacock, Philip Roberts, Zornitza Stark, Gabrielle Lemire, Yoko A Ito, Kym M Boycott, Michael T Geraghty, Jan Bert Klinken Show all

HUMAN MOLECULAR GENETICS | OXFORD UNIV PRESS | Published : 2022

DOI: 10.1093/hmg/ddac040

Abstract

Mitochondrial diseases are a group of inherited diseases with highly varied and complex clinical presentations. Here, we report four individuals, including two siblings, affected by a progressive mitochondrial encephalopathy with biallelic variants in the cardiolipin biosynthesis gene CRLS1. Three affected individuals had a similar infantile presentation comprising progressive encephalopathy, bull’s eye maculopathy, auditory neuropathy, diabetes insipidus, autonomic instability, cardiac defects and early death. The fourth affected individual presented with chronic encephalopathy with neurodevelopmental regression, congenital nystagmus with decreased vision, sensorineural hearing loss, failur..

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University of Melbourne Researchers

Zornitza Stark Author

David Thorburn Author

Gavin Reid Author

Related Projects (1)

Cutting the Fat: Photodissociation Mass Spectrometry for Lipidome Analysis

This project aims to develop and apply novel bioanalytical mass spectrometry-based methods and workflows to illuminate the otherwise hidden ..

Grants

Awarded by Mito Foundation

Awarded by National Health and Medical Research Council

Awarded by Australian Research Council

Awarded by US Department of Defense Congressionally Directed Medical Research Programs

Awarded by Ontario Genomics Institute

Funding Acknowledgements

Mito Foundation (G071 to R.G.L.), National Health and Medical Research Council (GNT1058442, GNT1045677, GNT1041582, GNT1023460, GNT1005030, GNT1043978 to A.F. and O.R.; GNT1155244 to D.R.T., GNT1113531), the Australian Research Council (DP180101656 to A.F. and O.R., and DP190102464 to G.E.R.), US Department of Defense Congressionally Directed Medical Research Programs (PR170396 to D.R.T.) and the Gift of Giving Lexus Ball Fund. M.S. is supported by a UWA Postgraduate Scholarship. The research studies for Family 2 were supported by the Care4Rare Canada Consortium funded by Genome Canada and the Ontario Genomics Institute (OGI-147), the Canadian Institutes of Health Research, Ontario Research Fund, Genome Alberta, Genome British Columbia, Genome Quebec, and Children's Hospital of Eastern Ontario Foundation. The research utilized equipment and support provided by the Queensland Metabolomics and Proteomics (Q-MAP) node, an initiative of the National Collaborative Research Infrastructure Strategy (NCRIS). Microscopy Australia at the Centre for Microscopy, Characterisation & Analysis, The University of Western Australia is funded by the University, State and Commonwealth Governments.