{
  "abstract": "FITM2 encodes fat storage-inducing transmembrane protein 2 (FIT2), a lipid diphosphatase in the ER that cleaves acyl-CoAs and is crucial for ER homeostasis. In humans, homozygous null mutations in FITM2 are associated with a syndrome characterized by deafness and dystonia. Here, we report two families presenting with late childhood-onset, slowly progressive limb spasticity, cerebellar features, and relatively preserved cognition, consistent with a complex hereditary spastic paraplegia (HSP) phenotype in whom exome sequencing revealed compound heterozygosity for FITM2 mutations. In each family, the affected probands carry one putative null allele and one G100R missense allele. Functional analyses demonstrated that the G100R allele is hypomorphic, with FIT2 protein levels reduced to 20% of wild type, leading to proportionately decreased enzyme activity. The occurrence of similar HSP disease phenotypes and the same hypomorphic mutation in these families suggests that the G100R mutation and its associated reduced enzyme activity represent a newly recognized clinical manifestation of FITM2 mutations, expanding the spectrum of conditions associated with this gene.",
  "abstract_shown": true,
  "affiliations": [
    "Neuromuscular Disorders Department UCL Queen Square Institute of Neurology London UK.",
    "Department of Neurology Great Ormond Street Hospital for Children London UK nhs.uk.",
    "Developmental Neurosciences Department UCL GOS Institute of Child Health London UK.",
    "Department of Molecular Metabolism Harvard T.H. Chan School of Public Health Boston USA harvard.edu.",
    "Department of Cell Biology Harvard Medical School Boston USA harvard.edu.",
    "Cell Biology Program Sloan Kettering Institute Memorial Sloan Kettering Cancer Center New York USA mskcc.org.",
    "Department of Molecular Genetics Genomedica Piraeus Greece.",
    "Neurogenetics Unit First Department of Neurology School of Medicine National and Kapodistrian University of Athens Eginition University Hospital Athens Greece uoa.gr.",
    "Department of Genetics for Rare Diseases Papageorgiou General Hospital Thessaloniki Greece papageorgiou-hospital.gr.",
    "Third Department of Pediatrics University General Hospital \"Attikon\" Athens Greece attikonhospital.gr.",
    "Department of Clinical and Movement Neurosciences UCL Queen Square Institute of Neurology London UK.",
    "Biomedical Research Foundation of the Academy of Athens (BRFAA) Athens Greece.",
    "Hematology Research Lab Clinical Experimental and Translational Research Center Biomedical Research Foundation Academy of Athens Athens Greece academyofathens.gr.",
    "Laboratory of Medical Genetics Medical School National and Kapodistrian University of Athens Athens Greece uoa.gr.",
    "Greek Genome Center Biomedical Research Foundation of the Academy of Athens Athens Greece academyofathens.gr.",
    "Department of Genetic Medicine and Development Medical School University of Geneva Geneva Switzerland unige.ch.",
    "1st Department of Neurology Eginitio Hospital National and Kapodistrian University of Athens Athens Greece uoa.gr.",
    "Howard Hughes Medical Institute New York USA hhmi.org."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 21,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ainara Salazar-Villacorta",
      "orcid": "0000-0002-5753-2687"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Laura M Bond"
    },
    {
      "affs": [
        5
      ],
      "name": "Leehyeon Kim",
      "orcid": "0000-0002-1266-7828"
    },
    {
      "affs": [
        6
      ],
      "name": "Katherine Anagnostopoulou"
    },
    {
      "affs": [
        0
      ],
      "name": "Annarita Scardamaglia",
      "orcid": "0009-0007-6013-4819"
    },
    {
      "affs": [
        7
      ],
      "name": "Eugenia Filippakopoulou",
      "orcid": "0000-0003-0638-6779"
    },
    {
      "affs": [
        8
      ],
      "name": "Athina Ververi",
      "orcid": "0000-0002-8393-4444"
    },
    {
      "affs": [
        0
      ],
      "name": "Stephanie Efthymiou",
      "orcid": "0000-0003-4900-9877"
    },
    {
      "affs": [
        9
      ],
      "name": "Argirios Dinopoulos"
    },
    {
      "affs": [
        10
      ],
      "name": "David Murphy"
    },
    {
      "affs": [
        7
      ],
      "name": "Chrisoula Kartanou",
      "orcid": "0000-0003-2032-2253"
    },
    {
      "affs": [
        11
      ],
      "name": "Dimitrios M Vrachnos"
    },
    {
      "affs": [
        12
      ],
      "name": "Theodoros Loupis"
    },
    {
      "affs": [
        13,
        14,
        15
      ],
      "name": "Perilikis Makrythanasis",
      "orcid": "0000-0002-3725-0113"
    },
    {
      "affs": [
        16
      ],
      "name": "Leonidas Stefanis",
      "orcid": "0000-0003-3569-8990"
    },
    {
      "affs": [
        7
      ],
      "name": "Georgia Karadima",
      "orcid": "0000-0001-7003-5717"
    },
    {
      "affs": [
        7
      ],
      "name": "Georgios Koutsis",
      "orcid": "0000-0002-8980-8377"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Marios Kaliakatsos"
    },
    {
      "affs": [
        0
      ],
      "name": "Henry Houlden",
      "orcid": "0000-0002-2866-7777"
    },
    {
      "affs": [
        5,
        17
      ],
      "name": "Tobias C Walther",
      "orcid": "0000-0003-1442-1327"
    },
    {
      "affs": [
        5
      ],
      "name": "Robert V Farese"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/2k8x5gf1zqraq.bib",
  "cited_by": 0,
  "doi": "10.1155/humu/5893503",
  "fulltext_url": "https://europepmc.org/articles/PMC13691184",
  "id": "2k8x5gf1zqraq",
  "issns": [
    "1059-7794",
    "1098-1004"
  ],
  "landing_url": "https://europepmc.org/article/MED/42920715",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2804|Hereditary Neurological Disorders"
    ]
  ],
  "openalex": "W7223391311",
  "pdf_url": "https://europepmc.org/articles/PMC13691184?pdf=render",
  "pmcid": "PMC13691184",
  "pmid": "42920715",
  "published": "2026-10-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/2k8x5gf1zqraq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:33Z",
      "native_id": "MED:42920715",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42920715"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Hereditary Neurological Disorders",
      "subfield": "neuroscience"
    }
  ],
  "title": "Partial Loss of FITM2 Function Causes Hereditary Spastic Paraplegia.",
  "title_text": "Partial Loss of FITM2 Function Causes Hereditary Spastic Paraplegia.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:33Z",
  "url": "https://research.draconitic.com/paper/2k8x5gf1zqraq",
  "venue": "Human mutation",
  "versions": []
}