French national reference center for mitochondrial diseases from children to adults (CARAMMEL)
The reference center for « mitochondrial diseases from children to adults » (CARAMMEL), located in the Necker-Enfants malades university hospital, coordinates the national CARAMMEL network, which is made up of 4 constitutive centers (Angers, Bordeaux, Strasbourg, Le Kremlin-Bicêtre) and 4 competence centers (Rouen, Caen, Créteil-Henri Mondor, Paris Lariboisière) dedicated to the diagnosis and treatment of patients with mitochondrial diseases.
The members of the Necker reference center are clinical and molecular geneticists, paediatricians, neuropaediatricians, adult neurologists, metabolists, radiologists, biochemists and researchers. The diversity of the professions represented reflects the extreme variety of clinical manifestations of mitochondriopathies which involve all medical specialities. The members of the reference center meet on a weekly basis in order to assess the files of patients seen during a consultation or hospitalisation at Necker, or files submitted to them by colleagues outside Necker.
This clinical activity feeds a high-level clinical and fundamental research activity.
This reference center is affiliated to the Filnemus rare disease healthcare network and to the EURO-NMD european reference network (ERN).
> Visit the national Carammel website
Keywords : Mitochondrial disease, mitochondrial myopathy, cardiomyopathy, ataxia, Leigh syndrome, respiratory chain, optic atrophy, mitochondrial DNA.
Medical
team
Head of the reference center
Pr Manuel Schiff
MD, PhD
Contact us
Talk to someone or make an appointment
Phone +33 1 44 49 51 64
or + 33 1 44 49 51 64
or + 33 1 44 49 51 53
> Send an email
> Send an email to the secretariat of the reference center
In case of emergency
- Expertise mission
- Development of recommendations or care protocols to promote good practices in patient care
- Dissemination and implementation of recommendations, protocols and procedures within the FILNEMUS healthcare network
- Participation in national and international working groups
- Coordination of a weekly multidisciplinary consultation meeting (RCP) in person and remotely with the participation of other reference centers of the CARAMMEL network
- Validation of indications for high-throughput sequencing for mitochondrial diseases in the SeqOIA platform
- Recourse mission
- Medical consultations, teleconsultations, hospitalizations
- Advice on files, local or remote
- Diagnosis announcement
- Off-label prescriptions and orphan drugs
- Postnatal, prenatal and preimplantation diagnostic tests
- Research and epidemiological surveillance mission
- Implementation of and participation in national and international funded research projects
- Dissemination of knowledge through :
- publications in national or international peer-reviewed journals
- communications in national or international conferences
- Evaluation of the recourse activity from a quantitative and qualitative point of view
- Participation in the collection of data in national or international databases
- Education and training mission
- Teaching medical, undergraduate and graduate students
- Training within the framework of continuous professional development (CPD)
- Hosting of students in connection with the « Genetics of mitochondrial diseases » research team of the IMAGINE university hospital institute at Necker in the framework of M1, M2, university, medical and pharmaceutical theses
- Writing of articles and books with educational content
- Leigh syndrome
- Kearns-Sayre syndrome
- Pearson syndrome
- Adult-onset CPEO with mitochondrial myopathy
- Leber hereditary optic neuropathy
- Kjer optic atrophy
- Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS)
- Mitochondrial NeuroGastroIntestinal Encephalomyopathy (MNGIE)
- Myoclonic Epilepsy with Ragged Red Fibers (MERRF)
- NARP syndrome
- Friedreich ataxia (FRDA)
Pediatrician
Pr Jean-Paul Bonnefont
MD, PhD
Pediatrician-Geneticist
Pr Arnold Munnich
MD, PhD
Geneticist and adult neurologist
Pr Benoit Funalot
MD, PhD
Pediatrician
Pr Pascale de Lonlay
MD, PhD
Radiologist
Pr Nathalie Boddaert
MD, PhD
Research director
Dr Agnès Rötig
PhD
Geneticist and neuropediatrician
Dr Giulia Barcia
MD, PhD
Metabolic pediatrician
Pr Manuel Schiff
MD, PhD
Neuropediatrician
Pr Isabelle Desguerre
MD, PhD
Pediatrician
Dr Claire-Marine Dufeu-Berat
MD
Geneticist
Pr Julie Steffann
MD, PhD
Neuropediatrician
Pr Pierre Landrieu
MD, PhD
Biologist
Zahra Assouline
PhD
Insofar as the natural history of mitochondrial diseases differs from one patient to another, and/or organ damage is associated in a non-systematic way, the structuring of therapeutic education is based on multidisciplinary skills for each child and at each moment.
The permanence of care is ensured by the site’s coordinating physician, or one of his assistants, who calls on organ specialists on a case-by-case basis depending on the clinical manifestations.
The child-adult transition is crucial: it is necessary to develop a network of referents in the different adult specialties.
As an example, a weekly genetic consultation has been developed at Necker, which is essentially a children’s hospital, and is provided by an adult neurogeneticist. He is responsible for referring patients leaving the pediatric age group to the various adult specialists.
- EJP-RD – Genomit 3, Mitochondrial Disorders: from a global registry to medical genomics, toward clinical trials – Imagine Institute, UMR1163 – in progress
- AFM – Deficient protein processing in mitochondrial diseases – Imagine Institute, UMR1163 – in progress
- Dillon Foundation – Design of an AAV-based gene therapy for mitochondrial disease caused by mutations in the RNA stability factor LRPPRC – Imagine Institute, UMR1163 – in progress
- DIM Thérapie génique – Thérapie génique de l’ataxie de Friedreich – Imagine Institute, UMR1163 – in progress
- DIM Thérapie génique – Gene therapy approach to treat mitochondrial diseases caused by defects in mitochondrial gene expression – Imagine Institute, UMR1163 – in progress
- Crosslab Institut Imagine – ImmunoMito – Defects of mitochondrial DNA maintenance and dysregulated immune response – Imagine Institute, UMR1163 – in progress
- MSD Avenir – Devo-Decode project – Decoding developmental disorders in humans – Imagine Institute, UMR1163 – in progress
- E-rare – Genomit 2, Mitochondrial Disorders: from a world-wide registry to medical genomics, toward molecular mechanisms and new therapies – Imagine Institute, UMR1163 – finalized
- AFAF – Homéostasie du fer dans des modèles cellulaires d’ataxie de Friedreich – Imagine Institute, UMR1163 – finalized
- AFM – An integrated approach for mitochondrial disorder therapeutics: from yeasts and worms to humans – Imagine Institute, UMR1163 – finalized
- Fondation Maladies Rares – Imagine Institute, UMR1163 – finalized
- AFM Mitochondrial replacement therapy against mtDNA disorders. Are we far from its clinical application? – Imagine Institute, UMR1163 – in progress
- IUD of Myology
Sorbonne University - European Master of Genetics
Paris University - M2 « GenE2 » and « Fundamental Microbiology»
Paris-Saclay - IUD in Fetal Medicine
Paris University - Master 2 Clinical research in fetal physiopathology
Paris University - Bachelor of Science in Biomedical Sciences
Paris University
2021
- Biallelic IARS2 mutations presenting as sideroblastic anemia.
Barcia G, Pandithan D, Ruzzenente B, Assouline Z, Pennisi A, Ormieres C, Besmond C, Roux CJ, Boddaert N, Desguerre I, Thorburn DR, Bratkovic D, Munnich A, Bonnefont JP, Rötig A, Steffann J.
Haematologica. 2021 106:1220-1225. doi: 10.3324/haematol.2020.270710. - Novel FARS2 variants in patients with early onset encephalopathy with or without epilepsy associated with long survival
Barcia G, Rio M, Assouline Z, Zangarelli C, Roux CJ, de Lonlay P, Steffann J, Desguerre I, Munnich A, Bonnefont JP, Boddaert N, Rötig A, Metodiev MD, Ruzzenente B.
Eur J Hum Genet. 2021 29:533-538. doi: 10.1038/s41431-020-00757-x. - Mitochondrial DNA mutations do not impact early human embryonic development.
Chatzovoulou K, Mayeur A, Gigarel N, Jabot-Hanin F, Hesters L , Munnich A, Frydman N, Bonnefont JP, Steffann J.
Mitochondrion 2021 May;58:59-63. doi: 10.1016/j.mito.2021.02.012. Epub 2021 Feb 24. - Cerebral blood flow and acute episodes of Leigh syndrome in neurometabolic disorders.
Loiselet K, Ruzzenente B, Roux CJ, Barcia G, Pennisi A, Desguerre I, Rötig A, Munnich A, Boddaert N.
Dev Med Child Neurol. 2021 63:705-711. doi: 10.1111/dmcn.14814. Epub 2021 Jan 28. - Defective palmitoylation of transferrin receptor triggers iron overload in Friedreich ataxia fibroblasts.
Petit F, Drecourt A, Dussiot M, Zangarelli C, Hermine O, Munnich A, Rötig A.
Blood. 2021 137:2090-2102. doi: 10.1182/blood.2020006987. - Phenotypic diversity of brain MRI patterns in mitochondrial aminoacyl-tRNA synthetase mutations.
Roux CJ, Barcia G, Schiff M, Sissler M, Levy R, Dangouloff-Ros V, Desguerre I, Edvardson S, Elpeleg O, Rötig A, Munnich A, Boddaert N.
Mol Genet Metab. 2021 133:222-229. doi: 10.1016/j.ymgme.2021.04.004. - Novel NDUFA12 variants are associated with isolated complex I defect and variable clinical manifestation.
Torraco A, Nasca A, Verrigni D, Pennisi A, Zaki MS, Olivieri G, Assouline Z, Martinelli D, Maroofian R, Rizza T, Di Nottia M, Invernizzi F, Lamantea E, Longo D, Houlden H, Prokisch H, Rötig A, Dionisi-Vici C, Bertini E, Ghezzi D, Carrozzo R, Diodato D.
Hum Mutat. 2021 Mar 14. doi: 10.1002/humu.24195. - A retrospective study on the efficacy of prenatal diagnosis for pregnancies at risk of mitochondrial DNA disorders.
Steffann J, Monnot S, Magen M, Assouline Z, Gigarel N, Ville Y, Salomon L, Bessiere B, Martinovic J, Rötig A, Bengoa J, Borghèse R, Munnich A, Barcia G, Bonnefont JP.
Genet Med. 2021 23:720-731. doi: 10.1038/s41436-020-01043-3. - Compromised mitochondrial quality control triggers lipin1-related rhabdomyolysis.
Yamina Hamel, François-Xavier Mauvais, Marine Madrange, Perrine Renard, Corinne Lebreton, Ivan Nemazanyy, Olivier Pellé, Nicolas Goudin, Xiaoyun Tang, Mathieu P Rodero, Caroline Tuchmann-Durand, Patrick Nusbaum, David N Brindley, Peter van Endert, Pascale de Lonlay
Cell Rep Med, 2021 Aug 17, PMID: 34467247 PMCID: PMC8385327 DOI: 10.1016/j.xcrm.2021.100370 - A Review of Multiple Mitochondrial Dysfunction Syndromes, Syndromes Associated with Defective Fe-S Protein Maturation.
Elise Lebigot, Manuel Schiff, Marie-Pierre Golinelli-Cohen
Biomedicines, 2021 Aug 10, PMID: 34440194 PMCID: PMC8393393 DOI: 10.3390/biomedicines9080989 - Variants in the MIPEP gene presenting with complex neurological phenotype without cardiomyopathy, impair OXPHOS protein maturation and lead to a reduced OXPHOS abundance in patient cells.
Juliette Pulman, Benedetta Ruzzenente, Martin Horak, Giulia Barcia, Nathalie Boddaert, Arnold Munnich, Agnès Rötig, Metodi D Metodiev
Mol Genet Metab, 2021 Nov, PMID: 34620555 DOI: 10.1016/j.ymgme.2021.09.005
2020
- Clinical, neuroimaging and biochemical findings in patients and patient fibroblasts expressing ten novel GFM1 mutations.
Barcia G, Rio M, Assouline Z, Zangarelli C, Gueguen N, Dumas VD, Marcorelles P, Schiff M, Slama A, Barth M, Hully M, de Lonlay P, Munnich A, Desguerre I, Bonnefont JP, Steffann J, Procaccio V, Boddaert N, Rötig A, Metodiev MD, Ruzzenente B.
Hum Mutat. 2020 41:397-402. doi: 10.1002/humu.23937. - Evidence of diaphragmatic dysfunction with severe alveolar hypoventilation syndrome in mitochondrial respiratory chain deficiency.
Barcia G, Khirani S, Amaddeo A, Assouline Z, Pennisi A, Boddaert N, Romero N, Desguerre I, Schiff M, Rötig A, Besmond C, Bonnefont JP, Munnich A, Fauroux B.
Neuromuscul Disord. 2020 30:593-598. doi: 10.1016/j.nmd.2020.06.002. - Improving post-natal detection of mitochondrial DNA mutations.
Barcia G, Assouline Z, Magen M, Pennisi A, Rötig A, Munnich A, Bonnefont JP, Steffann J.
Expert Rev Mol Diagn. 2020 20:1003-1008. doi: 10.1080/14737159.2020.1820326. - Bi-Allelic UQCRFS1 Variants Are Associated with Mitochondrial Complex III Deficiency, Cardiomyopathy, and Alopecia Totalis.
Gusic M, Schottmann G, Feichtinger RG, Du C, Scholz C, Wagner M, Mayr JA, Lee CY, Yépez VA, Lorenz N, Morales-Gonzalez S, Panneman DM, Rötig A, Rodenburg RJT, Wortmann SB, Prokisch H, Schuelke M.
Am J Hum Genet. 2020 106:102-111 - PRPS1 loss-of-function variants, from isolated hearing loss to severe congenital encephalopathy: New cases and literature review.
Mercati O, Abi Warde MT, Lina-Granade G, Rio M, Heide S, de Lonlay P, Ceballos-Picot I, Robert MP, Couloigner V, Beltrand J, Boddaert N, Rodriguez D, Rubinato E, Lapierre JM, Merlette C, Sanquer S, Rötig A, Prokisch H, Lyonnet S, Loundon N, Kaplan J, Bonnefont JP, Munnich A, Besmond C, Jonard L, Marlin S.
Eur J Med Genet. 2020 63:104033. doi: 10.1016/j.ejmg.2020.104033. - Heterogeneity of PNPT1 neuroimaging: mitochondriopathy, interferonopathy or both?
Pennisi A, Rötig A, Roux CJ, Lévy R, Henneke M, Gärtner J, Teke Kisa P, Sarioglu FC, Yiş U, Konczal LL, Burkardt DD, Wu S, Gaignard P, Besmond C, Hubert L, Rio M, Barcia G, Munnich A, Boddaert N, Schiff M.
J Med Genet. 2020 Nov 16, PMID: 33199448 DOI: 10.1136/jmedgenet-2020-107367 - The natural history of infantile mitochondrial DNA depletion syndrome due to RRM2B deficiency.
Nandaki Keshavan, Jose Abdenur, Glenn Anderson, Zahra Assouline, Giulia Barcia, Lamia Bouhikbar, Anupam Chakrapani, Maureen Cleary, Marta C. Cohen, François Feillet, Carl Fratter, Natalie Hauser, Tom Jacques, Amanda Lam, Helen McCullagh, Rahul Phadke, Agnès Rötig, Mark Sharrard, Mariella Simon, Conrad Smith, Ewen W. Sommerville, Robert W. Taylor, Wyatt W. Yue & Shamima Rahman
Genet Med, 2020 Jan, PMID: 31462754 DOI: 10.1038/s41436-019-0613-z - Sensory neuronopathy as a major clinical feature of mitochondrial trifunctional protein deficiency in adults.
Y Nadjar, S Souvannanorath, T Maisonobe, M Brisset, P De Lonlay, M Schiff, K Viala, A Boutron, G Nicolas, P Laforêt
Rev Neurol (Paris), 2020 May, PMID: 32253025 DOI: 10.1016/j.neurol.2019.11.011 - Loss of MTX2 causes mandibuloacral dysplasia and links mitochondrial dysfunction to altered nuclear morphology.
Sahar Elouej, Karim Harhouri, Morgane Le Mao, Genevieve Baujat, Sheela Nampoothiri, Hϋlya Kayserili, Nihal Al Menabawy, Laila Selim, Arianne Llamos Paneque, Christian Kubisch, Davor Lessel, Robert Rubinsztajn, Chayki Charar, Catherine Bartoli, Coraline Airault, Jean-François Deleuze, Agnes Rötig, Peter Bauer, Catarina Pereira, Abigail Loh, Nathalie Escande-Beillard, Antoine Muchir, Lisa Martino, Yosef Gruenbaum, Song-Hua Lee, Philippe Manivet, Guy Lenaers, Bruno Reversade, Nicolas Lévy & Annachiara De Sandre-Giovannoli
Nat Commun, 2020 Sep 11, PMID: 32917887 PMCID: PMC7486921 DOI: 10.1038/s41467-020-18146-9
2019
- Cytochrome c oxidase deficiency caused by biallelic SCO2 mutations in two sibs with cerebellar ataxia and progressive peripheral axonal neuropathy.
Barcia G, Assouline Z, Pennisi A, Gitiaux C, Schiff M, Boddaert N, Munnich A, Bonnefont JP, Rötig A.
Mol Genet Metab Rep. 2019 21:100528. doi: 10.1016/j.ymgmr.2019.100528. - Mitochondrial myopathy plus due to the variant m.586G > A in MT-TF.
Barcia G, Assouline Z, Pennisi A, Steffann J, Boddaert N, Gitiaux C, Rötig A, Bonnefont JP, Munnich A.
Mol Genet Metab Rep. 2019 21:100522. doi: 10.1016/j.ymgmr.2019.100522. - The natural history of infantile mitochondrial DNA depletion syndrome due to RRM2B deficiency.
Keshavan N, Abdenur J, Anderson G, Assouline Z, Barcia G, Bouhikbar L, Chakrapani A, Cleary M, Cohen MC, Feillet F, Fratter C, Hauser N, Jacques T, Lam A, McCullagh H, Phadke R, Rötig A, Sharrard M, Simon M, Smith C, Sommerville EW, Taylor RW, Yue WW, Rahman S.
Genet Med. 2019 Aug 29, PMID: 31462754 DOI: 10.1038/s41436-019-0613-z - Mutations in the MRPS28 gene encoding the small mitoribosomal subunit protein bS1m in a patient with intrauterine growth retardation, craniofacial dysmorphism and multisystemic involvement.
Pulman J, Ruzzenente B, Bianchi L, Rio M, Boddaert N, Munnich A, Rötig A, Metodiev MD.
Hum Mol Genet. 2019 28:1445-1462. doi: 10.1093/hmg/ddy441. - Expanding and Underscoring the Hepato-Encephalopathic Phenotype of QIL1/MIC13.
Russell BE, Whaley KG, Bove KE, Labilloy A, Lombardo RC, Hopkin RJ, Leslie ND, Prada C, Assouline Z, Barcia G, Bouchereau J, Chomton M, Debray D, Dorboz I, Durand P, Gaignard P, Habes D, Jardel C, Labarthe F, Lévy J, Lombès A, Mehler-Jacob C, Melki J, Menvielle L, Munnich A, Mussini C, Pichard S, Rio M, Rötig A, Sissaoui S, Slama A, Miethke AG, Schiff M.
Hepatology. 2019 Sep;70(3):1066-1070. doi: 10.1002/hep.30627. - Expanding the clinical spectrum of MTTF mutations
Barcia G, Assouline Z, Steffann J, Boddaert N, Gitiaux C, Rötig A, Bonnefont JP, Munnich A.
Mol Genet Metab Rep. 2019 ;21:100501. doi: 10.1016/j.ymgmr.2019.100501.
- Increased incidence of obstetric complications in women carrying mitochondrial DNA mutations: a retrospective cohort study in a single tertiary centre.
Kuleva M, Ben Miled S, Steffann J, Bonnefont JP, Rondeau S, Ville Y, Munnich A, Salomon LJ
BJOG. 2019;126:1372-1379 - Epilepsy with migrating focal seizures: KCNT1 mutation hotspots and phenotype variability
Barcia G, Chemaly N, Kuchenbuc d, Eisermann F, Gobin-Limballe S, Ciorna G, Macaya F, lambert L, Dubois T, Doummar D, Billette de Villemeur T, Villeneuve J, Barthez M, Nava C, Boddaert N, kaminska A, Bahi-Buisson N, Milh M, Auvin S, Bonnefont JP, Nabbout R
Neurol Genet 2019 ;5:e363
2018
- PRUNE1 Deficiency: Expanding the Clinical and Genetic Spectrum.
Alhaddad B, Schossig A, Haack TB, Kovács-Nagy R, Braunisch MC, Makowski C, Senderek J, Vill K, Müller-Felber W, Strom TM, Krabichler B, Freisinger P, Deshpande C, Polster T, Wolf NI, Desguerre I, Wörmann F, Rötig A, Ahting U, Kopajtich R, Prokisch H, Meitinger T, Feichtinger RG, Mayr JA, Jungbluth H, Hubmann M, Zschocke J, Distelmaier F, Koch J.
Neuropediatrics. 2018 49:330-338 - Pitfalls in molecular diagnosis of Friedreich ataxia.
Barcia G, Rachid M, Magen M, Assouline Z, Koenig M, Funalot B, Barnerias C, Rötig A, Munnich A, Bonnefont JP, Steffann J.
Eur J Med Genet. 2018 61:455-458. doi: 10.1016/j.ejmg.2018.03.004. - High predictive value of brain MRI imaging in primary mitochondrial respiratory chain deficiency.
de Beaurepaire I, Grévent D, Rio M, Desguerre I, de Lonlay P, Levy R, Dangouloff-Ros V, Bonnefont JP, Barcia G, Funalot B, Besmond C, Metodiev MD, Ruzzenente B, Assouline Z, Munnich A, Rötig A, Boddaert N.
J Med Genet. 2018 55:378-383. doi: 10.1136/jmedgenet-2017-105094. - Mitochondrial double-stranded RNA triggers antiviral signalling in humans.
Dhir A, Dhir S, Borowski LS, Jimenez L, Teitell M, Rötig A, Crow YJ, Rice GI, Duffy D, Tamby C, Nojima T, Munnich A, Schiff M, de Almeida CR, Rehwinkel J, Dziembowski A, Szczesny RJ, Proudfoot NJ.
Nature. 2018 560:238-242. doi: 10.1038/s41586-018-0363-0. - Impaired Transferrin Receptor Palmitoylation and Recycling in Neurodegeneration with Brain Iron Accumulation.
Drecourt A, Babdor J, Dussiot M, Petit F, Goudin N, Garfa-Traoré M, Habarou F, Bole-Feysot C, Nitschké P, Ottolenghi C, Metodiev MD, Serre V, Desguerre I, Boddaert N, Hermine O, Munnich A, Rötig A.
Am J Hum Genet. 2018 102:266-277. doi: 10.1016/j.ajhg.2018.01.003. - Bi-allelic Mutations in the Mitochondrial Ribosomal Protein MRPS2 Cause Sensorineural Hearing Loss, Hypoglycemia, and Multiple OXPHOS Complex Deficiencies.
Gardeitchik T, Mohamed M, Ruzzenente B, Karall D, Guerrero-Castillo S, Dalloyaux D, van den Brand M, van Kraaij S, van Asbeck E, Assouline Z, Rio M, de Lonlay P, Scholl-Buergi S, Wolthuis DFGJ, Hoischen A, Rodenburg RJ, Sperl W, Urban Z, Brandt U, Mayr JA, Wong S, de Brouwer APM, Nijtmans L, Munnich A, Rötig A, Wevers RA, Metodiev MD, Morava E.
Am J Hum Genet. 2018 102:685-695. doi: 10.1016/j.ajhg.2018.02.012. - Three human aminoacyl-tRNA synthetases have distinct sub-mitochondrial localizations that are unaffected by disease-associated mutations.
González-Serrano LE, Karim L, Pierre F, Schwenzer H, Rötig A, Munnich A, Sissler M.
J Biol Chem. 2018 293:13604-13615. doi: 10.1074/jbc.RA118.003400. - Biallelic Mutations in MRPS34 Lead to Instability of the Small Mitoribosomal Subunit and Leigh Syndrome.
Lake NJ, Webb BD, Stroud DA, Richman TR, Ruzzenente B, Compton AG, Mountford HS, Pulman J, Zangarelli C, Rio M, Boddaert N, Assouline Z, Sherpa MD, Schadt EE, Houten SM, Byrnes J, McCormick EM, Zolkipli-Cunningham Z, Haude K, Zhang Z, Retterer K, Bai R, Calvo SE, Mootha VK, Christodoulou J, Rötig A, Filipovska A, Cristian I, Falk MJ, Metodiev MD*, Thorburn DR*. * co-last authors
Am J Hum Genet. 2018 102:713. - NDUFB8 Mutations Cause Mitochondrial Complex I Deficiency in Individuals with Leigh-like Encephalomyopathy.
Piekutowska-Abramczuk D, Assouline Z, Mataković L, Feichtinger RG, Koňařiková E, Jurkiewicz E, Stawiński P, Gusic M, Koller A, Pollak A, Gasperowicz P, Trubicka J, Ciara E, Iwanicka-Pronicka K, Rokicki D, Hanein S, Wortmann SB, Sperl W, Rötig A, Prokisch H, Pronicka E, Płoski R, Barcia G, Mayr JA.
Am J Hum Genet. 2018 102:460-467 - Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency: is riboflavin supplementation effective?
Repp BM, Mastantuono E, Alston CL, Schiff M, Haack TB, Rötig A, Ardissone A, Lombès A, Catarino CB, Diodato D, Schottmann G, Poulton J, Burlina A, Jonckheere A, Munnich A, Rolinski B, Ghezzi D, Rokicki D, Wellesley D, Martinelli D, Wenhong D, Lamantea E, Ostergaard E, Pronicka E, Pierre G, Smeets HJM, Wittig I, Scurr I, de Coo IFM, Moroni I, Smet J, Mayr JA, Dai L, de Meirleir L, Schuelke M, Zeviani M, Morscher RJ, McFarland R, Seneca S, Klopstock T, Meitinger T, Wieland T, Strom TM, Herberg U, Ahting U, Sperl W, Nassogne MC, Ling H, Fang F, Freisinger P, Van Coster R, Strecker V, Taylor RW, Häberle J, Vockley J, Prokisch H, Wortmann S.
Orphanet J Rare Dis. 2018 13:120. doi: 10.1186/s13023-018-0784-8. - Inhibition of mitochondrial translation in fibroblasts from a patient expressing the KARS p.(Pro228Leu) variant and presenting with sensorineural deafness, developmental delay, and lactic acidosis.
Ruzzenente B, Assouline Z, Barcia G, Rio M, Boddaert N, Munnich A, Rötig A, Metodiev MD.
Hum Mutat. 2018 39:2047-2059. doi: 10.1002/humu.23657. - Segregation of mitochondrial DNA mutations in the human placenta: implication for prenatal diagnosis of mtDNA disorders.
Vachin P, Adda-Herzog E, Chalouhi G, Elie C, Rio M, Rondeau S, Gigarel N, Jabot Hanin F, Monnot S, Borghese R, Bengoa J, Ville Y, Rotig A, Munnich A, Bonnefont JP, Steffann J.
J Med Genet. 2018 55:131-136. doi: 10.1136/jmedgenet-2017-104615.
2017
- Mutations in MDH2, Encoding a Krebs Cycle Enzyme, Cause Early-Onset Severe Encephalopathy.
Ait-El-Mkadem S, Dayem-Quere M, Gusic M, Chaussenot A, Bannwarth S, François B, Genin EC, Fragaki K, Volker-Touw CL, Vasnier C, Serre V, van Gassen KL, Lespinasse F, Richter S, Eisenhofer G, Rouzier C, Mochel F, De Saint-Martin A, Abi Warde MT, de Sain-van der Velde MG, Jans JJ, Amiel J, Avsec Z, Mertes C, Haack TB, Strom T, Meitinger T, Bonnen PE, Taylor RW, Gagneur J, van Hasselt PM, Rötig A, Delahodde A, Prokisch H, Fuchs SA, Paquis-Flucklinger V.
Am J Hum Genet. 2017 100:151-159 - Compound heterozygosity for severe and hypomorphic NDUFS2 mutations cause non-syndromic LHON-like optic neuropathy.
Gerber S, Ding MG, Gérard X, Zwicker K, Zanlonghi X, Rio M, Serre V, Hanein S, Munnich A, Rotig A, Bianchi L, Amati-Bonneau P, Elpeleg O, Kaplan J, Brandt U, Rozet JM.
J Med Genet. 2017 54:346-356. doi: 10.1136/jmedgenet-2016-104212. - Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy.
Habarou F, Hamel Y, Haack TB, Feichtinger RG, Lebigot E, Marquardt I, Busiah K, Laroche C, Madrange M, Grisel C, Pontoizeau C, Eisermann M, Boutron A, Chrétien D, Chadefaux-Vekemans B, Barouki R, Bole-Feysot C, Nitschke P, Goudin N, Boddaert N, Nemazanyy I, Delahodde A, Kölker S, Rodenburg RJ, Korenke GC, Meitinger T, Strom TM, Prokisch H, Rotig A, Ottolenghi C, Mayr JA, de Lonlay P. Biallelic
Am J Hum Genet. 2017 101:283-290 - Genetic diagnosis of Mendelian disorders via RNA sequencing.
Kremer LS, Bader DM, Mertes C, Kopajtich R, Pichler G, Iuso A, Haack TB, Graf E, Schwarzmayr T, Terrile C, Koňaříková E, Repp B, Kastenmüller G, Adamski J, Lichtner P, Leonhardt C, Funalot B, Donati A, Tiranti V, Lombes A, Jardel C, Gläser D, Taylor RW, Ghezzi D, Mayr JA, Rötig A, Freisinger P, Distelmaier F, Strom TM, Meitinger T, Gagneur J, Prokisch H.
Nat Commun. 2017 8:15824 - FDXR Mutations Cause Sensorial Neuropathies and Expand the Spectrum of Mitochondrial Fe-S-Synthesis Diseases.
Paul A, Drecourt A, Petit F, Deguine DD, Vasnier C, Oufadem M, Masson C, Bonnet C, Masmoudi S, Mosnier I, Mahieu L, Bouccara D, Kaplan J, Challe G, Domange C, Mochel F, Sterkers O, Gerber S, Nitschke P, Bole-Feysot C, Jonard L, Gherbi S, Mercati O, Ben Aissa I, Lyonnet S, Rötig A, Delahodde A, Marlin S.
Am J Hum Genet. 2017 101:630-637 - No correlation between mtDNA amount and methylation levels at the CpG island of POLG exon 2 in wild-type and mutant human differentiated cells.
Steffann J, Pouliet A, Adjal H, Bole C, Fourrage C, Martinovic J, Rolland-Galmiche L, Rotig A, Tores F, Munnich A, Bonnefont JP.
J Med Genet. 2017 54:324-329. doi: 10.1136/jmedgenet-2016-104335. - Segregation of mitochondrial DNA mutations in the human placenta: implication for prenatal diagnosis of mtDNA disorders.
Vachin P, Adda-Herzog E, Chalouhi G, Elie C, Rio M, Rondeau S, Gigarel N, Jabot Hanin F, Monnot S, Borghese R, Bengoa J, Ville Y, Rotig A, Munnich A, Bonnefont JP, Steffann J.
J Med Genet. 2018 55:131-136. doi: 10.1136/jmedgenet-2017-104615. - Biallelic variants in WARS2 encoding mitochondrial tryptophanyl-tRNA synthase in six individuals with mitochondrial encephalopathy.
Wortmann SB, Timal S, Venselaar H, Wintjes LT, Kopajtich R, Feichtinger RG, Onnekink C, Mühlmeister M, Brandt U, Smeitink JA, Veltman JA, Sperl W, Lefeber D, Pruijn G, Stojanovic V, Freisinger P, V Spronsen F, Derks TG, Veenstra-Knol HE, Mayr JA, Rötig A, Tarnopolsky M, Prokisch H, Rodenburg RJ.
Hum Mutat. 2017 38:1786-1795
2016
- High incidence and variable clinical outcome of cardiac hypertrophy due to ACAD9 mutations in childhood.
Collet M, Assouline Z, Bonnet D, Rio M, Iserin F, Sidi D, Goldenberg A, Lardennois C, Metodiev MD, Haberberger B, Haack T, Munnich A, Prokisch H, Rötig A.
Eur J Hum Genet. 2016 24:1112-6. doi: 10.1038/ejhg.2015.264. - Biallelic PPA2 Mutations Cause Sudden Unexpected Cardiac Arrest in Infancy.
Guimier A, Gordon CT, Godard F, Ravenscroft G, Oufadem M, Vasnier C, Rambaud C, Nitschke P, Bole-Feysot C, Masson C, Dauger S, Longman C, Laing NG, Kugener B, Bonnet D, Bouvagnet P, Di Filippo S, Probst V, Redon R, Charron P, Rötig A, Lyonnet S, Dautant A, de Pontual L, di Rago JP, Delahodde A, Amiel J.
Am J Hum Genet. 2016 99:666-73 - Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA Processing and Multiple Respiratory Chain Deficiencies.
Metodiev MD, Thompson K, Alston CL, Morris AAM, He L, Assouline Z, Rio M, Bahi-Buisson N, Pyle A, Griffin H, Siira S, Filipovska A, Munnich A, Chinnery PF, McFarland R, Rötig A, Taylor RW.
Am J Hum Genet. 2016 May 5;98(5):993-1000. doi: 10.1016/j.ajhg.2016.03.010. - Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA Processing and Multiple Respiratory Chain Deficiencies.
Metodiev MD, Thompson K, Alston CL, Morris AA, He L, Assouline Z, Rio M, Bahi-Buisson N, Pyle A, Griffin H, Siira S, Filipovska A, Munnich A, Chinnery PF, McFarland R, Rötig A, Taylor RW.
Am J Hum Genet. 2016 99:246. doi: 10.1016/j.ajhg.2016.06.013. - Combined use of Saccharomyces cerevisiae, Caenorhabditis elegans and patient fibroblasts leads to the identification of clofilium tosylate as a potential therapeutic chemical against POLG-related diseases.
Pitayu L, Baruffini E, Rodier C, Rötig A, Lodi T, Delahodde A.
Hum Mol Genet. 2016 25:715-27 - Mouse models for mitochondrial diseases.
Ruzzenente B, Rötig A, Metodiev MD.
Hum Mol Genet. 2016 2016 25(R2):R115-R122 - Mutations in Complex I Assembly Factor TMEM126B Result in Muscle Weakness and Isolated Complex I Deficiency.
Sánchez-Caballero L*, Ruzzenente B*, Bianchi L, Assouline Z, Barcia G, Metodiev MD, Rio M, Funalot B, van den Brand MA, Guerrero-Castillo S, Molenaar JP, Koolen D, Brandt U, Rodenburg RJ, Nijtmans LG, Rötig A. * co-first authors
Am J Hum Genet. 2016, 99:208-16.
PARTICIPATION IN SCIENTIFIC EVENTS
- Julie Steffann co-organizer ENMC Leigh 2022 Amsterdam
- Manuel Schiff co-organizer ENMC Leigh 2022 Amsterdam (https://www.enmc.org/download/leigh-syndrome-spectrum-genetic-causes-natural-history-and-preparing-for-clinical-trials/).
- JP Bonnefont 2023 HCERES evaluation of the research activity on mitochondrial diseases at Angers university hospital
ORAL COMMUNICATIONS AT INTERNATIONAL CONFERENCES
- Agnès Rötig. Leigh syndrome, Experience in France. ENMC workshop on “Genetic Epidemiology and Clinical Trial Readiness in Encephalomyopathy of Leigh Syndrome”, 16 Octobre et 20 Décembre 2020, 9 Juillet 2021.
- Agnès Rötig. Abnormal regulation of transferrin receptor in NBIA. 7 th International Symposium on NBIA and related disorders, 1-3 Octobre 2020, on line.
- Julie Steffann: “PGD for mtDNA disorders; success and challenge. The French experience”. Taskforce on « Nuclear Transfer for mitochondrial diseases and infertility 2021 Gent Belgium
- Julie Steffann: Developping guidelines for management of reproductive options for families with maternally inherited mtDNA disease. ENMC Leigh 2021 Amsterdam
- Julie Steffann: “PGD for mitochondrial DNA disorder: feasibility and concerns”. The 5th World Congress on Controversies in preconception, preimplantation, and prenatal genetic diagnosis (CoGEN) Paris 2020
Contact information
Necker-Enfants malades university Hospital
> Genomic medicine of rare diseases department
Molecular genetics laboratory
149 rue de Sèvres
75743 PARIS Cedex 15
> Pediatric welcome booklet
> Adult patients welcome booklet
In Necker, the reference center for mitochondrial diseases from children to adults (CARAMMEL) in brief …
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patients followed at least once a year*
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medical consultations*
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day hospitalizations*
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fully hospitalized patients*
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patients trained in therapeutic education*
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teleconsultation procedures*
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ongoing research projects*
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university courses*
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publications*
* data valid for 2022