Swiss Family with Dominant Stargardt Disease Caused by a Recurrent Mutation in the ELOVL4 Gene

Tran, Hoai Viet; Moret, Emmanuelle; Vaclavik, Véronika; Marcelli, F.; Abitbol, Marie; Munier, Francis L.

doi:10.1055/s-0042-102585

Cited by 4 publications

(3 citation statements)

References 10 publications

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“…Again, the net result was a truncation of 45 amino acids from the WT ELOVL4 protein. This mutation has recently been reported in a Swiss family with STGD3 (Tran et al, 2016) that is not related to the Belgian family reported by Maugeri. In 2016, Bardak et al (2016), reported two genetic variants in exon 6 in a Turkish family with the Stargardt-like disease phenotype.…”

Section: Discovery Of Multiple Mutations In Fatty Acid Elongase-4 (Elmentioning

confidence: 56%

ELOVL4: Very long-chain fatty acids serve an eclectic role in mammalian health and function

Hopiavuori

Anderson

Agbaga

2019

Progress in Retinal and Eye Research

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ELO ngation of V ery L ong chain fatty acids- 4 (ELOVL4) is an elongase responsible for the biosynthesis of very long chain (VLC, ≥C28) saturated (VLC-SFA) and polyunsaturated (VLC-PUFA) fatty acids in brain, retina, skin, Meibomian glands, and testes. Fascinatingly, different mutations in this gene have been reported to cause vastly different phenotypes in humans. Heterozygous inheritance of seven different mutations in the coding sequence and 5’ untranslated region of ELOVL4 causes autosomal dominant Stargardt-like macular dystrophy (STGD3), while homozygous inheritance of three more mutant variants causes severe seizures with ichthyosis, hypertonia, and even death. Some recent studies have described heterozygous inheritance in yet another three mutant ELOVL4 variants, two that cause spinocerebellar ataxia-34 (SCA34) with erythrokeratodermia (EKV) and one that causes SCA34 without EKV. We identified the specific enzymatic reactions catalyzed by ELOVL4 and, using a variety of genetically engineered mouse models, have actively searched for the mechanisms by which ELOVL4 impacts neural function and health. In this review, we critically compare and contrast the various animal model and case studies involving ELOVL4 deficiency via either mutation or deletion, and the resulting consequences on neuronal health and function in both the retina and central nervous system.

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Section: Discovery Of Multiple Mutations In Fatty Acid Elongase-4 (Elmentioning

confidence: 56%

ELOVL4: Very long-chain fatty acids serve an eclectic role in mammalian health and function

Hopiavuori

Anderson

Agbaga

2019

Progress in Retinal and Eye Research

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“…#600110) is a rare dominant form due to mutations in the elongation of very long-chain fatty acids-like 4 (ELOVL4) gene on chromosome 6q16. [5][6][7][8] ELOVL4 plays a fundamental role in the synthesis of very long-chain polyunsaturated fatty acids (VLC-PUFA). 9,10 VLC-PUFA make up a considerable part of phosphatidylcholine (PC) in the outer segment of both cell types of photoreceptors, suggesting a relevant role in the correct folding of disk rim and in cones and rods membrane fluidity.…”

Section: Stgd3 (Online Mendelian Inheritance In Man [Omim]mentioning

confidence: 99%

Stargardt Phenotype Associated With Two ELOVL4 Promoter Variants and ELOVL4 Downregulation: New Possible Perspective to Etiopathogenesis?

Donato

Scimone

Rinaldi

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…The mutations in the ELOVL4 (the elongation of very long chain fatty acids) gene resulted in Stargardt macular dystrophy and early childhood blindness [ 39 ]. ELOVL4 encodes a membrane protein targeted to the ER, which is an enzyme involved in the generation of long-chain fatty acids [ 40 , 41 ]. Not only do photoreceptors express high levels of ELOVL4 , but other types of cells in the eye have been found to express ELOVL4 as well [ 42 ].…”

Section: Disturbance Of Proteostasis and Er Stress In Retinal Degementioning

confidence: 99%

Neuroprotective Strategy in Retinal Degeneration: Suppressing ER Stress-Induced Cell Death via Inhibition of the mTOR Signal

Fan

Sun

Liu

et al. 2017

IJMS

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The retina is a specialized sensory organ, which is essential for light detection and visual formation in the human eye. Inherited retinal degenerations are a heterogeneous group of eye diseases that can eventually cause permanent vision loss. UPR (unfolded protein response) and ER (endoplasmic reticulum) stress plays an important role in the pathological mechanism of retinal degenerative diseases. mTOR (the mammalian target of rapamycin) kinase, as a signaling hub, controls many cellular processes, covering protein synthesis, RNA translation, ER stress, and apoptosis. Here, the hypothesis that inhibition of mTOR signaling suppresses ER stress-induced cell death in retinal degenerative disorders is discussed. This review surveys knowledge of the influence of mTOR signaling on ER stress arising from misfolded proteins and genetic mutations in retinal degenerative diseases and highlights potential neuroprotective strategies for treatment and therapeutic implications.

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Swiss Family with Dominant Stargardt Disease Caused by a Recurrent Mutation in the ELOVL4 Gene

Cited by 4 publications

References 10 publications

ELOVL4: Very long-chain fatty acids serve an eclectic role in mammalian health and function

ELOVL4: Very long-chain fatty acids serve an eclectic role in mammalian health and function

Stargardt Phenotype Associated With Two ELOVL4 Promoter Variants and ELOVL4 Downregulation: New Possible Perspective to Etiopathogenesis?

Neuroprotective Strategy in Retinal Degeneration: Suppressing ER Stress-Induced Cell Death via Inhibition of the mTOR Signal

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