Isolated juvenile macular dystrophy without posterior column ataxia associated with FLVCR1 mutation

Lachmann, Eva S; Mautone, Luca; Dulz, Simon

doi:10.1080/13816810.2021.1970196

Cited by 3 publications

(5 citation statements)

References 13 publications

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“…FLVCR1-mediated choline uptake is essential for life as its complete loss leads to embryonic lethality, suggesting that the salvage pathway cannot completely compensate in vivo. Similarly, patients with missense mutations in FLVCR1 present with posterior column ataxia and retinitis pigmentosa (PCARP), an autosomal recessive neurodegenerative syndrome characterized by loss of retinal function and subsequent degeneration of the posterior columns of the spinal cord from proprioception loss [10][11][12][13] . Interestingly, the photoreceptor cells of the retina have high affinity for choline and require an abundance of phospholipids to maintain the large membranous surface area of the outer segment [49][50][51] .…”

Section: Discussionmentioning

confidence: 99%

“…1g). FLVCR1 is a plasma membrane transporter previously characterized as a heme exporter 9 and has been implicated in the rare autosomal-recessive disorder posterior column ataxia and retinitis pigmentosa (PCARP) [10][11][12][13] . CHKA catalyzes the production of phosphocholine through phosphorylation of choline.…”

Section: An Integrative Genetic Analysis Associates Serum Metabolites...mentioning

confidence: 99%

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Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

Kenny

Khan

Son

et al. 2022

Preprint

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Genome-wide association studies (GWAS) of serum metabolites have the potential to uncover genes that influence human metabolism. Here, we combined an integrative genetic analysis associating serum metabolites to membrane transporters with a coessentiality map of metabolic genes. This analysis revealed a connection between feline leukemia virus subgroup C cellular receptor 1 (FLVCR1) - a plasma membrane protein - and phosphocholine, a downstream metabolite of choline metabolism. Loss of FLVCR1 in human cells and in mice strongly impairs choline metabolism due to a block in choline import. Consistently, CRISPR-based genetic screens identified several components of the membrane phospholipid machinery as synthetic lethal with FLVCR1 loss. Finally, cells lacking FLVCR1 exhibit mitochondrial defects and upregulate the integrated stress response (ISR) through heme regulated inhibitors kinase (HRI). Altogether, these findings identify FLVCR1 as a universal mediator of choline transport in mammals and provide a platform to discover substrates for unknown metabolite transporters.

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Section: Discussionmentioning

confidence: 99%

Section: An Integrative Genetic Analysis Associates Serum Metabolites...mentioning

confidence: 99%

Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

Kenny

Khan

Son

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…Sural biopsy confirmed loss of myelinated and unmyelinated fibers 3,13,14,18,22 . Previous studies reported 29 variants of FLVCR1, including splice site, missense, nonsense, deletion, duplication, and loss 3,10,12–29 . In this study, we identified novel FLVCR1 mutations in an adult patient with tremors, sensory neuropathy, and retinitis pigmentosa.…”

Section: Introductionmentioning

confidence: 53%

“…Insidious visual loss is another cardinal feature in patients, which is common in FLVCR1‐related diseases 3,13,14,16,25,26 . The ocular symptoms did not deteriorate with disease development.…”

Section: Discussionmentioning

confidence: 99%

“…3,13,14,18,22 Previous studies reported 29 variants of FLVCR1, including splice site, missense, nonsense, deletion, duplication, and loss. 3,10,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] In this study, we identified novel FLVCR1 mutations in an adult patient with tremors, sensory neuropathy, and retinitis pigmentosa.…”

Section: Introductionmentioning

confidence: 99%

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Novel mutations in FLVCR1 cause tremors, sensory neuropathy with retinitis pigmentosa

Chu

et al. 2023

Neuropathology

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The mutations of the feline leukemia virus subgroup C receptor‐related protein 1 (FLVCR1) cause ataxia with retinitis pigmentosa. Recent studies indicated a large variation in the phenotype of FLVCR1‐associated diseases. In this report, we describe an adult male who manifested first with tremors in his third decade, followed by retinitis pigmentosa, sensory ataxia, and sensory neuropathy in his fourth decade. While retinitis pigmentosa and sensory ataxia are well‐recognized features of FLVCR1‐associated disease, tremor is rarely described. Whole‐exome sequencing revealed novel compound heterozygous pathogenic FLVCR1 variants: c.498 G > A; p.(Trp166*) and c.369 T > G; p.(Phe123Leu). In addition, we have highlighted the ultrastructural abnormalities of the sural biopsy in this patient.

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Integrative genetic analysis identifies FLVCR1 as a plasma-membrane choline transporter in mammals

et al. 2023

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Isolated juvenile macular dystrophy without posterior column ataxia associated with FLVCR1 mutation

Cited by 3 publications

References 13 publications

Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

Integrative genetic analysis identifies FLVCR1 as an essential component of choline transport in mammals

Novel mutations in FLVCR1 cause tremors, sensory neuropathy with retinitis pigmentosa

Integrative genetic analysis identifies FLVCR1 as a plasma-membrane choline transporter in mammals

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