AMFR dysfunction causes autosomal recessive spastic paraplegia in human that is amenable to statin treatment in a preclinical model.

"data availability rna-seq of nscs is publicly available through the national center for biotechnology information (ncbi) gene expression omnibus (geo) under accession number gse202141. codes used for data analysis are available via github: https://github com/barakatlab/amfr_paper git . data availability rna-seq of nscs is publicly available through the national center for biotechnology information (ncbi) gene expression omnibus (geo) under accession number gse202141"

"codes used for data analysis are available via github: https://github com/barakatlab/amfr_paper git ."

"Declarations Conflict of interestAMBA, CP, RT, VK, and PB are employees of Centogene GmbH. TBP is an employee of GeneDx LLC. The remaining authors declare no conflict of interest. Conflict of interest AMBA, CP, RT, VK, and PB are employees of Centogene GmbH. TBP is an employee of GeneDx LLC. The remaining authors declare no conflict of interest."

"We thank all patients and families for participation in this study, and all members of the Barakat lab for helpful discussions. RD and YS are supported by a China Scholarship Council (CSC) PhD Fellowship (201906300026 to RD, 202008500138 to YS) for their PhD studies at the Erasmus Medical Center, Rotterdam, The Netherlands. SLZ is supported in her PhD studies by Stichting 12q. Some results reported here were generated using funding received from the Solve-RD project within the European Rare Disease Models & Mechanisms Network (RDMM-Europe). The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No 779257. Part of this research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK, and the Medical Research Council have also funded research infrastructure. The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support. SB was supported by the NIHR Manchester Biomedical Research Centre (NIHR203308) and acknowledges the grant funding support of the Spastic Paraplegia Foundation (USA). NKa was supported by the King Salman Center for Disability Research through Award No. RAC: #2180-004. RR and STA were supported by funding from King Abdullah University of Science and Technology (KAUST), Office of Sponsored Research (OSR), FCC/1/1976-25 and REI/1/4446-01. For computational protein modelling, the resources of the Supercomputing Laboratory at KAUST were used. The Barakat lab was supported by the Netherlands Organisation for Scientific Research (ZonMw Veni, grant 91617021; ZonMw Vidi, grant 09150172110002), an Erasmus MC Fellowship 2017, and Erasmus MC Human Disease Model Award 2018. Funding bodies did not have any influence on study design, results, and data interpretation or final manuscript."