An autosomal dominant neurological disorder caused by de novo variants in FAR1 resulting in uncontrolled synthesis of ether lipids.
Sacha FerdinandusseKirsty McWalterHeleen Te BrinkeLodewijk IJlstPetra M MooijerJos P N RuiterAlida E M van LintMia Pras-RavesEric WeverFrancisca MillanMaria J Guillen SacotoAmber BegtrupMark TarnopolskyLauren BradyRoger L LaddaSusan L SellCatherine B NowakJessica DouglasCuixia TianElizabeth UlmSeth PerlmanArlene V DrackKaren ChongNicole MartinJennifer BraultElly BrokampCamilo ToroWilliam A GahlEllen F MacnamaraLynne Wolfenull nullQuinten WaisfiszPetra J G ZwijnenburgAlban ZieglerMagalie BarthRosemarie SmithSara EllingwoodDeborah Gaebler-SpiraSomayeh BakhtiariMichael C KruerAntoine H C van KampenRonald J A WandersHans R WaterhamDavid CassimanFrederic M VazPublished in: Genetics in medicine : official journal of the American College of Medical Genetics (2020)
Heterozygous de novo variants affecting the Arg480 residue of FAR1 lead to an autosomal dominant disorder with a different disease mechanism than that of recessive FAR1 deficiency and a diametrically opposed biochemical phenotype. Our findings show that for patients with spastic paraparesis and bilateral cataracts, FAR1 should be considered as a candidate gene and added to gene panels for hereditary spastic paraplegia, cerebral palsy, and juvenile cataracts.