Translational research in neurogenetic diseases (NRGEN)


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The team gathers together researchers interested in a continuum of overlapping neurogenetic disorders covering spinocerebellar degenerations (ataxias, spastic paraplegias), motor neuron diseases (amyotrophic lateral sclerosis, hereditary spastic paraplegias, neuropathies) and neurodegeneration with brain iron accumulations (NBIA).
Our goal is to dissect the molecular bases of these neurogenetic diseases with the long-term goal of developing specific therapies, which are lacking for almost all of them. To this end, we use a combination of genetic analyses (exome, genome, repeat expansion detection), phenotype-genotype correlations, biomarker searches and functional analyses (cellular, yeast and mouse models).

Selected publications

  • Méreaux JL, Banneau G, Papin M, Coareli G, Valter R, Raymond L, Kol B, Ariste O, Parodi L, Tissier L, Mairey M, Ait-Said S, Gautier C, Guillaud-Bataille M, the French SPATAX clinical network, Forlani S, de la Grange P, Brice A, Vazza G, Durr A, Leguern E, Stevanin G. Clinical and genetic spectra of 1550 index patients with hereditary spastic paraplegia. BRAIN 2022 (online January 4)
  • Pujol C, Legrand A, Parodi L, Thomas P, Mochel F, Saracino D, Coarelli G, Aradjanski M, Popovic M, Valet M, Villain N, Elshafie S, Issa M, Zuily S, Renaud M, Marelli-Tosi C, Legendre M, Trimouille A, Kemlin I, Mathieu S, Gleeson JG, Lamari F, Galatolo D, Alkouri R, Tse C, Rodriguez D, Ewenczyk C, Fellmann F, Kuntzer T, Blond E, El Hachimi KH, Darios F, Seyer A, Gazi A, Giavalisco P, Perin S, Boucher JL, Le Corre L, Santorelli FM, Goizet C, Zaki M, Picaud S, Mourier A, Steculorum S, Mignot C, Durr A, Trifunovic A, and Stevanin G. Implication of Folate Deficiency in CYP2U1 loss of function. J Exp Med 2021, 218(11):e20210846.
  • Durand CM, Dhers L, Tesson C, Tessa A, Fouillen L, Jacquere S, Raymond L, Coupry I, Benard G, Darios F, El-Hachimi KH, Astrea G, Rivier F, Banneau G, Pujol C, Lacombe D, Durr A, Babin PJ, Santorelli FM, Pietrancosta N, Boucher JL, Mansuy D, Stevanin G, Goizet C. CYP2U1 activity is altered by missense mutations in hereditary spastic paraplegia 56. Hum Mut 2018, 39:140-151.
  • Coutelier M, Goizet C, Durr A, Habarou F, Morais S, Dionne-Laporte A, Tao F, Konop J, Stoll M, Charles P, Jacoupy M, Matusiak R, Alonso I, Tallaksen C, Mairey M, Kennerson M, Gaussen M, Schule R, Janin M, Morice-Picard F, Durand CM, Depienne C, Calvas P, Coutinho P, Saudubray JM, Rouleau G, Brice A, Nicholson G, Darios F, Loureiro JL, Zuchner S, Ottolenghi C, Mochel F, Stevanin G. Alteration of ornithine metabolism leads to dominant and recessive hereditary spastic paraplegia. Brain 2015, 138: 2191-2205.
  • Tesson C, Nawara M, Salih MAM, Rossignol R, Zaki M, Al Balwi M, Schule R, Mignot C, Obre E, Bouhouche A, Santorelli FM, Durand CM, Caballero-Oteyza A, El-Hachimi KH, Al Drees A, Bouslam N, Lamari F, El Malik SA, Kabiraj MM, Seidahmed MZ, Esteves T, Gaussen M, Monin ML, Gyapay G, Lechner D, Gonzalez M, Depienne C, Mochel F, Lavie J, Schols L, Lacombe D, Yahyaoui M, Al Abdulkareem I, Zuchner S, Yamashita A, Benomar A, Goizet C, Durr A, Gleeson JG, Darios F, Brice A, Stevanin G. Alteration of fatty acid-metabolizing enzymes affects mitochondrial functions in hereditary spastic paraplegia. Am J Hum Genet 2012, 91: 1051-1064.
  • Goizet C, Depienne C, Benard G, Boukhris A, Mundwiller E, Solé G, Coupry I, Pilliod J, Martin-Négrier ML, Fedirko E, Forlani S, Cazeneuve C, Hannequin D, Charles P, Feki I, Pinel JF, Ouvrad-Hernandez AN, Lyonnet S, Ollagnon-Roman E, Yaouanq J, Toutain A, Dussert C, Fontaine B, Leguern E, Lacombe D, Durr A, Rossignol R, Brice A, Stevanin G. REEP1 Mutations in SPG31: Frequency, Mutational Spectrum and Potential Association with Mitochondrial Morpho-functional Dysfunction. Hum Mut 2011, 32:1118-1127.
  • Goizet C, Boukhris A, Durr A, Beetz C, Truchetto J, Tesson C, Tsaousidou M, Forlani S, Guyant-Maréchal L, Fontaine B, Guimarães J, Isidor B, Chazouillères O, Wendum D, Grid D, Chevy F, Chinnery PF, Coutinho P, Azulay JF, Feki I, Mochel F, Wolf C, Mhiri C, Crosby A, Brice A, Stevanin G. CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5. Brain 2009, 132:1789-1600.
  • Goizet C, Boukhris A, Maltete D, Guyant-Maréchal L, Truchetto J, Mundwiller E, Hanein S, Jonveaux P, Roelens F, Loureiro J, Godet E, Forlani S, Melki J, Auer-Grumbach M, Fernandez JC, Martin-Hardy P, Sibon I, Sole G, Orignac I, Mhiri C, Coutinho P, Durr A, Brice A, Stevanin G. SPG15 is the second most common cause of hereditary spastic paraplegia with thin corpus callosum. Neurology 2009, 73:1111-1119.
  • Hanein S, Martin E, Boukhris A, Byrne P, Goizet C, Hamri A, Benomar A, Lossos A, Denora P, Fernandez J, Elleuch N, Forlani S, Durr A, Feki I, Huntchinson M, Santorelli FM, Mhiri C, Brice A, Stevanin G. Identification of the SPG15 gene, encoding spastizin, as a frequent cause of complicated autosomal recessive spastic paraplegia including Kjellin syndrome. Am J Hum Genet 2008, 82:992-1002
  • Stevanin G, Santorelli F, Azzedine H, Coutinho P, Chomilier J, Denora PS, Martin E, Ouvrard-Hernandez AM, Tessa A, Bouslam N, Lossos A, Charles P, Loureiro JL, Elleuch N, Confavreux C, Cruz VT, Ruberg M, Leguern E, Grid D, Tazir M, Fontaine B, Filla A, Bertini E, Durr A, Brice A (*co-first authors). Mutations in the SPG11 gene, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nature Genet 2007, 39 (3): 366-372.
Team leader
Giovanni Stevanin

Cyril Goizet

Team member(s)

Cyril Goizet (Team leader)
Giovanni Stevanin (Team leader)

Chercheurs, Praticiens hospitaliers...

Isabelle Coupry (Researcher)
Jean-Paul Lasserre (Assistant professor)

Ingénieur(e)s, technicien(ne)s