Journal article

Cerebral hypomyelination associated with biallelic variants of FIG4

Guy M Lenk, Ian R Berry, Chloe A Stutterd, Moira Blyth, Lydia Green, Gayatri Vadlamani, Daniel Warren, Ian Craven, Miriam Fanjul-Fernandez, Victoria Rodriguez-Casero, Paul J Lockhart, Adeline Vanderver, Cas Simons, Susan Gibb, Simon Sadedin, Susan M White, John Christodoulou, Olga Skibina, Jonathan Ruddle, Tiong Y Tan Show all

HUMAN MUTATION | WILEY | Published : 2019

Abstract

The lipid phosphatase gene FIG4 is responsible for Yunis-Varón syndrome and Charcot-Marie-Tooth disease Type 4J, a peripheral neuropathy. We now describe four families with FIG4 variants and prominent abnormalities of central nervous system (CNS) white matter (leukoencephalopathy), with onset in early childhood, ranging from severe hypomyelination to mild undermyelination, in addition to peripheral neuropathy. Affected individuals inherited biallelic FIG4 variants from heterozygous parents. Cultured fibroblasts exhibit enlarged vacuoles characteristic of FIG4 dysfunction. Two unrelated families segregate the same G > A variant in the +1 position of intron 21 in the homozygous state in one fa..

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Grants

Awarded by National Institute of General Medical Sciences


Awarded by National Heart, Lung and Blood Institute


Awarded by NHMRC Postgraduate Scholarship


Awarded by NATIONAL HUMAN GENOME RESEARCH INSTITUTE


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Funding Acknowledgements

National Institute of General Medical Sciences, Grant/Award Number: R01 GM24872; National Human Genome Research Institute, National Eye Institute, and National Heart, Lung and Blood Institute, Grant/Award Number: UM1 HG008900; NHMRC Postgraduate Scholarship, Grant/Award Number: GNT1133266; Neurogenetics Fellowship from Thyne-Reid Foundation and Macquarie Foundation; NHMRC Independent Research Institute Infrastructure Support Scheme; Victorian State Government Operational Infrastructure Program