@article{1306956d0d6b4b1b8e15fa0d8dad02cb,
title = "ACO2 homozygous missense mutation associated with complicated hereditary spastic paraplegia",
abstract = "Objective: To identify the clinical characteristics and genetic etiology of a family affected with hereditary spastic paraplegia (HSP). Methods: Clinical, genetic, and functional analyses involving genome-wide linkage coupled to wholeexome sequencing in a consanguineous family with complicated HSP. Results: A homozygous missense mutation was identified in the ACO2 gene (c.1240T>G p.Phe414Val) that segregated with HSP complicated by intellectual disability and microcephaly. Lymphoblastoid cell lines of homozygous carrier patients revealed significantly decreased activity of the mitochondrial aconitase enzyme and defective mitochondrial respiration. ACO2 encodes mitochondrial aconitase, an essential enzyme in the Krebs cycle. Recessive mutations in this gene have been previously associated with cerebellar ataxia. Conclusions: Our findings nominate ACO2 as a disease-causing gene for autosomal recessive complicated HSP and provide further support for the central role of mitochondrial defects in the pathogenesis of HSP.",
author = "Bouwkamp, {Christian G.} and Zaid Afawi and Aviva Fattal-Valevski and Krabbendam, {Inge E.} and Stefano Rivetti and Rafik Masalha and Marialuisa Quadri and Breedveld, {Guido J.} and Hanna Mandel and Tailakh, {Muhammad Abu} and Beverloo, {H. Berna} and Giovanni Stevanin and Alexis Brice and {Van IJcken}, {Wilfred F.J.} and Vernooij, {Meike W.} and Dolga, {Amalia M.} and {De Vrij}, {Femke M.S.} and Vincenzo Bonifati and Kushner, {Steven A.}",
note = "Funding Information: The Article Processing Charge was funded by the authors. Funding Information: This study was funded in part by the Netherlands Organization for Scientific Research (NWO) and Netherlands Organisation for Health Research and Development (ZonMw) to S.A.K. and V.B., the Royal Netherlands Academy of Arts and Sciences (KNAW) Sara van Dam Foundation to C.G.B. and Z.A., the NeuroBasic-PharmaPhenomics consortium to S.A.K., and Stichting ParkinsonFonds (The Netherlands) to V.B. Publisher Copyright: {\textcopyright} 2018 The Author(s).",
year = "2018",
month = apr,
day = "1",
doi = "10.1212/NXG.0000000000000223",
language = "English",
volume = "4",
journal = "Neurology: Genetics",
issn = "2376-7839",
publisher = "Lippincott Williams and Wilkins",
number = "2",
}