Different Mutations in ELOVL4 Affect Very Long Chain Fatty Acid Biosynthesis to Cause Variable Neurological Disorders in Humans

  • Martin-Paul Agbaga
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 854)


All mammalian cell membranes are characterized by amphipathic lipid molecules that interact with proteins to confer structural and functional properties on the cell. The predominant lipid species are phospholipids, glycolipids, sphingolipids and cholesterol. These lipids contain fatty acids with variable hydrocarbon chain lengths between C14-C40, either saturated or unsaturated, that are derived from diet, synthesized de novo, or elongated from shorter chain fatty acids by fatty acid elongase enzymes. One member of the family of elongases, ELOngation of Very Long chain fatty acids-4 (ELOVL4), mediates the biosynthesis of both saturated and unsaturated very long chain fatty acids (VLC-FA; > C26) in the retina, meibomian gland, brain, skin, and testis. Different mutations in ELOVL4 cause tissue-specific maculopathy and/or neuro-ichthyotic disorders. The goal of this mini-review is to highlight how different mutations in ELOVL4 can cause variable phenotypic disorder, and propose a possible mechanism, based on the role of fatty acids in membranes, which could explain the different phenotypes.


Retinal degeneration Very long chain polyunsaturated fatty acids (VLC-PUFA) Elongation of very long chain fatty acids-4 (ELOVL4) Autosomal dominant Stargardt-like macular dystrophy Spinocerebellar ataxia (SCA) Erythrokeratodermia (EKV) 



Supported in part by grants from Hope for Vision, Knight Templar Eye Foundation Inc., and BrightFocus Foundation Inc., to MPA; NIH/NEI (EY04149 and EY21725 and the Foundation Fighting Blindness to my mentor, Robert E. Anderson, MD, PhD; and Research to Prevent Blindness, Inc. Thanks to Professor Anderson for his valuable comments and suggestions.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Ophthalmology, Dean McGee Eye InstituteUniversity of Oklahoma Health Sciences CenterOklahoma CityUSA

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