English (United Kingdom)   French (Fr)

Presentation

Clinical Research Group 1  « Mitochondrial diseases and mtDNA instability »


Pr Véronique PAQUIS-FLUCKLINGER, PU-PH1, Team Leader


Summary

Despite the majority of mitochondrial respiratory chain (MRC) components are nuclear-encoded, each mitochondrion contains 2 to 10 copies of a small (16569bp), circular, double-stranded DNA molecule. Mitochondrial diseases can be secondary to mutations either in the mitochondrial or in the nuclear genome and are responsible for a large variety of clinical syndromes. In the team, we are studying mitochondrial disorders and mainly those associated with mtDNA instability. We have shown that the origin of the instability may be exceptionally dependent on mtDNA itself by describing, for the first time, an unstable mutation in a mitochondrial gene encoding a complex I subunit (MT-ND6), which is responsible for Maternally Inherited Diabetes and Deafness (MIDD) (Bannwarth et al., 2011). Nevertheless, in most cases, human diseases associated with loss of mtDNA copies (depletion) or accumulation of multiple mtDNA deletions have an autosomal mode of inheritance, indicating that a defect in a nuclear gene is responsible for mtDNA instability. Indeed, the factors involved in mtDNA maintenance are encoded by nuclear genes and imported into mitochondria. Mutations in any of these genes may disturb mtDNA maintenance mechanisms and cause either quantitative or qualitative mtDNA molecular lesions. A few number of defective genes has been identified but, in most patients, genes and molecular mechanisms responsible for mtDNA alterations remain unknown.

figure_2_anglais

Premature aging in mice accumulating mtDNA mutations due to genetic inactivation of the mitochondrial polymerase proof reading activity (Mutator mice)

From Aleksandra Trifunovic et al.
Premature ageing in mice expressing defective mitochondrial DNA polymerase.
Nature 429, 417-423 (2004)


Mitochondrial myopathy with mtDNA instability

A-B. Histopathology with Gomori modified trichrome (A) showing RRFs and COX/SDH stain (B) revealing COX-deficient fibres, which are recognized by the prevalent blue stain.

C. Ultrastructure of skeletal muscle showing accumulation of lipid droplets and abnormal enlarged mitochondria with paracristallin inclusions. Original magnification: x12000.

D-E. Molecular analysis. Long-range PCR (D) and Southern blot (E) analysis revealing multiple deletion bands in addition to wild-type fragments. M: lambda HindIII/EcoRI (left) and 1Kb DNA ladder (right). C: control individual. P: patient. From Rouzier et al.,  Brain, 2012

Fragmentation of the mitochondrial network in fibroblasts
of a patient carrying a MFN2 mutation
Representative images are shown a color code highlights
the connectivity of the mitochondrial network.
A. Control individual. B. Patient. From Rouzier et al., Brain, 2012.

Research Project



Research Project

Our aim is to identify new genes and mechanisms involved in mtDNA instability disorders by 2 different approaches: (i) the study of patients and families affected by mitochondrial disorders associated with multiple mtDNA deletions or depletion and, (ii) the analysis of candidate genes encoding proteins involved in mtDNA maintenance in mouse model system


  • Identification of new genes responsible for mitochondrial disorders by whole exome sequencing

This work is made in direct collaboration with the Department of Medical Genetics and the Reference Centre for Mitochondrial Diseases (CHU of Nice, Archet 2 hospital), both managed by Véronique Paquis-Flucklinger. In this Centre, we collected a large series of patients with MRC defects. This situation allows a direct link between basic and medical research. The research team benefits from the collection of patients and the expertise of referring clinicians. The recent identification of MFN2, involved in the mitochondrial fusion, as a new gene associated with "mtDNA breakage syndrome" (Rouzier et al., 2012), illustrates the value of this collaboration.


  • Analysis of mtDNA instability in mouse model system

This is another approach used in the laboratory. For example, we are currently studying a protein involved in mtDNA metabolism through the analysis of KO mice. The animals developed a mitochondrial myopathy after 1 year of age with respiratory chain deficiency and accumulation of mtDNA deletions. KO mice exhibited a significantly lower daily running distance compared to wild-type animals, indicating muscle weakness. We find that the mitochondrial isoform encoded by this gene, generated via downstream alternative translation initiation (dATI), was present inside mitochondria and bound to mtDNA in vivo. Furthermore, gene inactivation caused a deficiency in repair of oxidative  mitochondrial DNA damage, thus confirming the role of this protein in mtDNA maintenance. These results open new avenues for the exploration of patients with mtDNA instability disorders and for the study of thid protein that plays a critical role in the maintenance of mtDNA stability, possibly preventing age-associated accumulation of mtDNA mutations.




Research Group

Research Group


PAQUIS-FLUCKLINGER Véronique, PU-PH, Team Leader
Tel (Medical School) : +33 (0)4 93 37 77 30, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it
Tel (Hospital)          : +33 (0)4 92 03 64 55, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it


AUGE Gaëlle, Technician CHU
Tel : +33 (0)4 92 03 64 59, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

BANNWARTH Sylvie, MCU-PH CHU
Tel : +33 (0)4 93 37 77 22, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

BERG-ALONSO Laetitia, PhD Student
Tel : +33 (0)4 93 37 77 27, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it     

CHAUSSENOT Annabelle, PH, Neurologist
Tel : +33 (0)4
92 03 64 59, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

FELIX Marjorie, AJT Université

Tel : +33 (0)4 93 37 70 15,  E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it


FRAGAKI-MOMMIER Konstanina, IR CHU
Tel : +33 (0)4 92 03 64 59, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

FRANÇOIS Bérengère, Master2 R

Tel : +33 (0)4 93 37 77 22, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it


GENIN Emmanuelle, CD CR UNS

Tel : +33 (0)4 93 37 77 22,  E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it


LESPINASSE Françoise, IE1 CNRS
Tel : +33 (0)4 93 37 77 22, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

MICHIELS Jean-François, PU-PH1
Tel : +33 (0)4 92 03 77 65, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

QUERE Manal, IE CHU

Tel : +33 (0)4 92 03 64 59, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it


ROUZIER Cécile, PH CHU

SAADI Samira, IR CHU
Tel : +33 (0)4 92 03 64 59, E-mail : This e-mail address is being protected from spambots. You need JavaScript enabled to view it

(March 2016)


    Publications

    Publications


    2016


    Bannwarth S, Berg-Alonso L, Augé G, Fragaki K, Kolesar JE, Lespinasse F, Lacas-Gervais S, Burel Vandenbos F, Villa E,

    Belmonte F, Michiels JF, Ricci JE, Gherardi R, Harrington L, Kaufman BA, Paquis-Flucklinger V.

    Inactivation of Pif1 helicase causes a mitochondrial myopathy in mice.

    Mitochondrion 2016 Feb 23 pii: S1567-7249(16)30008-3.      

            

    Fragaki, Chaussenot A, Benoist JF, Ait-El-Mkadem S, Bannwarth S, Rouzier C, Cochaud C, Paquis-Flucklinger V.

    Coenzyme Q10 defects may be associated with a deficiency of Q10-independent mitochondrial respiratory chain complexes.

    Biol Res 2016; Jan 8;49(1):4.


    2015


    Genin EC, Plutino M, Bannwarth S, Villa E, Cisneros-Barroso E, Roy M, Ortega-Vila B, Fragaki K, Lespinasse F, Pinero-Martos E,

    Auge G, Moore D, Burte F, Lacas-Gervais S, Kageyama Y, Itoh K, Yu-Wai-Man P, Sesaki H, Ricci JE, Vives-Bauza C, Paquis-Flucklinger V.

    CHCHD10 mutations promote loss of mitochondrial cristae junctions with defect in mitochondrial genome maintenance and apoptosis.

    EMBO Mol Med 2015 ; Dec 14;8(1):58-72  (Citation core facility PICMI IRCAN).


    Bannwarth S, Ait-El-Mkadem S, Chaussenot A, Genin EC, Lacas-Gervais S, Fragaki K, Berg-Alonso L, Kageyama Y, Serre V,

    Moore D, Verschueren A, Rouzier C, Le Ber I, Augé G, Cochaud C, Lespinasse F, N'Guyen K, de Septenville A, Brice A,

    Yu-Wai-Man P, Sesaki H, Pouget J, Paquis-Flucklinger V. Reply: High prevalence of CHCHD10 mutations in patients with

    frontotemporal dementia from China.

    Brain 2015 ; Dec 30. pii: awv368.


    Ait-El-Mkadem S, Chaussenot A, Bannwarth S, Paquis-Flucklinger V.

    CHCHD10-Related Disorders. 2015 Jul In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet].

    Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK304142/


    Dayem-Quere M, Giuliano F, Massol C, Piche M, Paquis-Flucklinger V, Karmous-Benailly H.

    De novo 4q duplication/deletion in a fetus with a congenital heart defect.

    Am J Med Genet A 2015; Aug;167A(8):1932-6.

     

    Morel G, Rouzier C, Chaussenot A, Ait-El-Mkadem S, Bannwarth S, Genin EC, Augé G, Chabrol B, Pouget J, Soriani MH,

    Sacconi S, Paquis-Flucklinger V. CHCHD10 mutations are not a common cause of SMN1-negative type III-IV

    spinal motor atrophy.

    Annals Neurol 2015; 78:831.


    Bannwarth S, Ait-El-Mkadem S, Chaussenot A, Genin EC, Lacas-Gervais S, Fragaki K, Berg-Alonso L, Kageyama Y,

    Serre V, Moore D, Verschueren A, Rouzier C, Le Ber I, Augé G, Cochaud C, Lespinasse F, N'Guyen K, de Septenville A,

    Brice A, Yu-Wai-Man P, Sesaki H, Pouget J, Paquis-Flucklinger V. Reply: Is CHCHD10 Pro34Ser pathogenic for

    frontotemporal dementia and amyotrophic lateral sclerosis?

    Brain 2015; May 7. pii: awv116


    Bannwarth S, Ait-El-Mkadem S, Chaussenot A, Genin EC, Lacas-Gervais S, Fragaki K,  Berg-Alonso L, Kageyama Y,

    Serre V, Moore D, Verschueren A, Rouzier C, Le Ber I, Augé G, Cochaud C, Lespinasse F, N’Guyen K, de Septenville A,

    Brice A, Yu Wai Man P, Sesaki H, Pouget J, Paquis-Flucklinger V. Reply: A distinct clinical phenotype in a German

    kindred with motor neuron disease carrying a CHCHD10 mutation.

    Brain; 2015 Feb 12. pii: awv015

     

    Bannwarth S, Ait-El-Mkadem S, Chaussenot A, Genin EC, Lacas-Gervais S, Fragaki K,  Berg-Alonso L, Kageyama Y,

    Serre V, Moore D, Verschueren A, Rouzier C, Le Ber I, Augé G, Cochaud C, Lespinasse F, N’Guyen K, de Septenville A,

    Brice A, Yu Wai Man P, Sesaki H, Pouget J, Paquis-Flucklinger V. Reply: CHCHD10 mutations in Italian sporadic ALS patients.

    Brain 2015; Jan 8. pii: awu385



    2014


    Plutino M, Chaussenot A, Ait-El-Mkadem S, Bannwarth S, Genin EC, Rouzier C, Augé G, Sacconi S, Pouget J, Paquis-Flucklinger V.

    Letter to the Editor on a paper by Hsiao C-T, Tsai P-C, Liao Y-C, Lee Y-C, Soong B-W. C9ORF72 repeat expansion is not a

    significant cause of late-onset cerebellar ataxia syndrome.

    J Neurol Sci 2014; 347:322-324.


    Bannwarth S, Ait-El-Mkadem S, Chaussenot A, Genin EC, Lacas-Gervais S, Fragaki K,  Berg-Alonso L, Kageyama Y, Serre V,

    Moore D, Verschueren A, Rouzier C, Le Ber I, Augé G, Cochaud C, Lespinasse F, N’Guyen K, de Septenville A, Brice A,

    Yu Wai Man P, Sesaki H, Pouget J, Paquis-Flucklinger V.

    Reply: Are CHCHD10 mutations indeed associated with familial amyotrophic lateral sclerosis ?

    Brain 2014; Dec;137(Pt 12):e314  


    Bannwarth S, Ait-El-Mkadem S, Chaussenot A, Genin EC, Lacas-Gervais S, Fragaki K,  Berg-Alonso L, Kageyama Y,

    Serre V, Moore D, Verschueren A, Rouzier C, Le Ber I, Augé G, Cochaud C, Lespinasse F, N’Guyen K, de Septenville A,

    Brice A, Yu Wai Man P, Sesaki H, Pouget J, Paquis-Flucklinger V.

    Reply: Mutations in the CHCHD10 gene are a common cause of familial amyotrophic lateral sclerosis.

    Brain 2014; Dec;137(Pt 12):e312


    Bannwarth S, Ait-El-Mkadem S, Chaussenot A, Genin EC, Lacas-Gervais S, Fragaki K,  Berg-Alonso L, Kageyama Y,

    Serre V, Moore D, Verschueren A, Rouzier C, Le Ber I, Augé G, Cochaud C, Lespinasse F, N’Guyen K, de Septenville A,

    Brice A, Yu Wai Man P, Sesaki H, Pouget J, Paquis-Flucklinger V.

    Reply: Two novel mutations in conserved codons indicate that CHCHD10 is a motor neuron disease gene.

    Brain 2014 ; Dec;137(Pt 12):e310


    Chaussenot A, Le Ber I, Ait-El-Mkadem S, Camuzat A, de Septenville A, Bannwarth S, Genin EC, Serre V, Augé G,

    The French research network on FTD and FTD-ALS, Brice A, Pouget J, Paquis-Flucklinger V. 

    Screening of CHCHD10 in a French cohort confirms the involvement of this gene in FTD-ALS.

    Neurobiology of Aging 2014; Dec;35(12):2884.e1-4


    Bannwarth S*, Ait-El-Mkadem S*, Chaussenot A, Genin EC, Lacas-Gervais S, Fragaki K,  Berg-Alonso L, Kageyama Y,

    Serre V, Moore D, Verschueren A, Rouzier C, Le Ber I, Augé G, Cochaud C, Lespinasse F, N’Guyen K, de Septenville A,

    Brice A, Yu Wai Man P, Sesaki H, Pouget J, Paquis-Flucklinger V. *Equal participation.

    A mitochondrial origin for frontotemporal dementia and amyotrophic lateral sclerosis through CHCHD10 involvement.

    Brain 2014; 137:2329-45


    Chaussenot A, Rouzier C, Quere M, Plutino M, Ait-El-Mkadem S, Bannwarth S, Barth M, Dollfus H, Charles P, Nicolino M,

    Chabrol B, Vialettes B, Paquis-Flucklinger V.

    Mutation update and uncommon phenotypes in a French cohort of 96 patients with WFS1-related disorders.

    Clin Genet 2014; May 29.doi:10.1111/cge.12437


    Chaussenot A, Paquis-Flucklinger V.

    An overview of neurological and neuromucular signs in mitochondrial diseases.

    Rev Neurol 2014; 170:323-38



    2013


    Farmer A, Aymé S, de Heredia ML, Maffei P, McCafferty S, Młynarski W, Nunes V, Parkinson K, Paquis-Flucklinger V,

    Rohayem J, Sinnott R, Tillmann V, Tranebjaerg L, Barrett TG.

    EURO-WABB: an EU rare diseases registry for Wolfram syndrome, Alström syndrome and Bardet-Biedl syndrome.

    BMC Pediatr 2013; Aug 27;13:130.


    Bannwarth S, Procaccio V, Lebre AS, Jardel C, Chaussenot C, Hoarau C, Maoulida H, Charrier N, Gai X, Xie HM, Ferre M,

    Fragaki K, Hardy G, Mousson de Camaret B, Marlin S, Dhaenens CM, Slama A, Rocher C, Bonnefont JP, Rötig A, Aoutil N,

    Gilleron M, Desquiret-Dumas V, Reynier P, Ceresuela J, Jonard L, Devos A, Espil-Taris C, Martinez D, Gaignard P,

    Le Quan Sang KH, Amati-Bonneau P, Falk MJ, Florentz C, Chabrol B, Durand-Zaleski I, Paquis-Flucklinger V.

    Prevalence of rare mitochondrial DNA mutations in mitochondrial disorders.

    J Med Genet 2013; 50:704-14


    Rouzier C, Chaussenot A, Serre V, Fragaki K, Bannwarth S, Ait-El-Mkadem S, Attarian S, Kaphan E, Cano A, Delmont E,

    Sacconi S, Mousson de Camaret B, Rio M, Lebre AS, Jardel C, Deschamps R, Richelme C, Pouget J, Chabrol B, Paquis-Flucklinger V.

    Interest of QMPSF analysis in the detection of large intragenic POLG1 rearrangements through the study of a large French cohort.

    Eur J Hum Genet 2013; 22:542-50


    Ribière C, Kaboré FA, Chaussenot A, Paquis-Flucklinger V, Lenne-Aurier K, Gaillet S, Boissier R, Karsenty G.

    Bladder-sphincter disorders associated with Wolfram syndrome.

    Prog Urol 2013; Jun;23(8):519-23.


    Bocquet B, Lacroux A, Surget MO, Baudoin C, Marquette V, Manes G, Hebrard M, Sénéchal A, Delettre C, Roux AF,

    Claustres M, Dhaenens CM, Rozet JM, Perrault I, Bonnefont JP, Kaplan J, Dollfus H, Amati-Bonneau P, Bonneau D,

    Reynier P, Audo I, Zeitz C, Sahel JA, Paquis-Flucklinger V, Calvas P, Arveiler B, Kohl S, Wissinger B, Blanchet C,

    Meunier I, Hamel CP.

    Relative frequencies of inherited retinal dystrophies and optic neuropathies in Southern France: assessment of

    21-year data management.

    Ophthalmic Epidemiol 2013;20(1):13-25.


    Ait-El-Mkadem S*, Fragaki K*, Chaussenot A, Gire C, Mengual R, Bonesso L, Bénéteau M, Ricci J-E, Desquiret-Dumas V,

    Procaccio V, Rötig A, Paquis-Flucklinger V. *Equal participation.

    Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency.

    Eur J Hum Genet 2013; 21:528-34.


    2012


    Bannwarth S, Figueroa A, Fragaki K, Destroismaisons L, Lacas-Gervais S, Lespinasse F, Vandenbos F, Pradelli LA, Ricci JE,

    Rötig A, Michiels JF, Vande Velde C, Paquis-Flucklinger V.

    The human MSH5 (MutS Homolog 5) protein localizes to

    mitochondria and protects the mitochondrial genome from oxidative damage.

    Mitochondrion 2012; 12:654-665


    Caietta E, Cano A, Halbert C, Hugonenq C, Mancini J, Milh M, Lépine A, Villeneuve N, Chaussenot A, Paquis-Flucklinger V,

    Chabrol B.

    Epilepsy and mitochondrial diseases : retrospective study on 53 epileptic children.

    Arch Pediatr 2012; 19:794-802.


    Rouzier C, Bannwarth S, Chaussenot A, Chevrollier A, Verschueren A, Bonello-Palot N, Fragaki K, Cano A, Pouget J,

    Pellissier JF, Procaccio V, Chabrol B, Paquis-Flucklinger V.

    The MFN2 gene is responsible for mitochondrial DNA instability and optic atrophy ‘plus’ phenotype.

    Brain 2012; 135: 23-34.


    Kichine E, Rozé V, Di Cristofaro J, Taulier D, Navarro A, Streichemberger E, Decarpentrie F, Metzler-Guillemain C,

    Lévy N, Chiaroni J, Paquis-Flucklinger V, Fellmann F, Mitchell MJ.

    HSFY genes and the P4 palindrome in the AZFb interval of the human Y chromosome are not required for spermatocyte maturation.

    Hum Reprod 2012; 27:615-24.


    Titah SM, Meunier I, Blanchet C, Lopez S, Rondouin G, Lenaers G, Amati-Bonneau P, Reynier P, Paquis-Flucklinger V, Hamel CP.

    Cataract as a phenotypic marker for a mutation in WFS1, the Wolfram syndrome gene.

    Eur J Ophthalmol 2012; 22:254-8.



    2011


    Bannwarth S, Abbassi M, Valéro R, Fragaki, K, Dubois N, Vialettes B, Paquis-Flucklinger V.

    A novel unstable mutation in mitochondrial DNA responsible for maternally inherited diabetes and deafness.

    Diabetes Care 2011; 34:2591-2593.


    Fragaki K, Cano A, Chaussenot A, Rouzier C, Bannwarth S, Caruba C, Chabrol B, Paquis-Flucklinger V.

    Fatal heart failure associated with coenzyme Q10 OXPHOS deficiency in an infant with propionic academia.

    Mitochondrion 2011; 11:533-6.


    Chaussenot A, Bannwarth S, Rouzier C, Vialettes B, Ait El Mkadem S, Chabrol B, Cano A, Labauge P, Paquis-Flucklinger V.

    Neurologic features and genotype-phenotype correlation in Wolfram syndrome.

    Annals Neurol 2011; 69 : 501-8.


    Lebre AS, Rio M, Faivre d'Arcier L, Vernerey D, Landrieu P, Slama A, Jardel C, Laforêt P, Rodriguez D, Dorison N,

    Galanaud D, Chabrol B, Paquis-Flucklinger V, Grévent D, Edvardson S, Steffann J, Funalot B, Villeneuve N,

    Valayannopoulos V, de Lonlay P, Desguerre I, Brunelle F, Bonnefont JP, Rötig A, Munnich A, Boddaert N.

    A common pattern of brain MRI imaging in mitochondrial diseases with complex I deficiency.

    J Med Genet 2011; 48:16-23.


    Burel-Vandenbos F, Benchetrit M, Miquel C, Fontaine D, Auvergne R, Lebrun-Frenay C, Cardot-Leccia N, Michiels JF,

    Paquis-Flucklinger V, Virolle T. EGFR immunolabeling pattern may discriminate low-grade gliomas from gliosis.

    J Neurooncol 2011; 102:171-8.


    Ninove L, Daniel L, Gallou J, Cougard PA, Charpentier A, Viard L, Roquelaure B, Paquis-Flucklinger V, de Lamballerie X, Zandotti C, Charrel RN.

    Fatal case of Reye's syndrome associated with H3N2 influenza virus infection and salicylate intake in a 12-year-old patient.

    Clin Microbiol Infect 2011; 17:95-7.


    2010


    Rouzier C, Le Guédard-Méreuze S, Fragaki K, Serre V, Miro J, S. Tuffery-Giraud, A. Chaussenot, S. Bannwarth, C.

    Caruba, E. Ostergaard, J.F. Pellissier, C. Richelme, C. Espil, B. Chabrol, Paquis-Flucklinger V.

    The severity of phenotype linked to SUCLG1 mutations could be correlated with residual amount of SUCLG1 protein.

    J Med Genet 2010; 47:670-676.


    Labauge P, Renard D, Chaussenot A, Paquis-Flucklinger V.

    Neurological picture.Wolfram syndrome associated with leukoencephalopathy.

    J Neurol Neurosurg Psychiatry 2010; 81:928.


    Lahaye F, Lespinasse F, Staccini P, Palin L, Paquis-Flucklinger V, Santucci-Darmanin S.

    hMSH5 is a nucleocytoplasmic shuttling protein whose stability depends on its subcellular localization.

    Nucleic Acids Res 2010; 38:3655-71.


    Nishigaki Y, Ueno H, Coku J, Koga Y, Fujii T, Sahashi K, Nakano K, Yoneda M, Nonaka M, Tang L, Liou CW,

    Paquis-Flucklinger V, Harigaya Y, Ibi T, Goto Y, Hosoya H, DiMauro S, Hirano M, Tanaka M.

    Extensive screening system using suspension array technology to detect mitochondrial DNA point mutations.

    Mitochondrion 2010; 10:300-8.


    2009


    • Fragaki K, Procaccio V, Bannwarth S, Serre V, O'Hearn S, Potluri P, Augé G, Casagrande F, Caruba C, Lambert JC, Paquis-Flucklinger, V. A neonatal polyvisceral failure linked to a de novo homoplasmic mutation in the mitochondrially encoded cytochrome b gene. Mitochondrion, 9:346-52 (2009)

    • Fromont I, Nicoli F, Valéro R, Felician O, Lebail B, Lefur Y, Mancini J, Paquis-Flucklinger, V., Cozzone PJ, Vialettes B. Brain anomalies in maternally inherited diabetes and deafness syndrome. J Neurol, 256:1696-704 (2009).

    • Bannwarth S, Procaccio V, Paquis-Flucklinger, V. Rapid identification of unknown heteroplasmic mitochondrial DNA mutations with mismatch-specific surveyor nuclease. Methods Mol Biol, 554:301-13 (2009).

    • Laloi-Michelin M, Meas T, Ambonville C, Bellanné-Chantelot C, Beaufils S, Massin P, Vialettes B, Gin H, Timsit J, Bauduceau B, Bernard L, Bertin E, Blickle JF, Cahen-Varsaux J, Cailleba A, Casanova S, Cathebras P, Charpentier G, Chedin P, Crea T, Delemer B, Dubois-Laforgue D, Duchemin F, Ducluzeau PH, Bouhanick B, Dusselier L, Gabreau T, Grimaldi A, Guerci B, Jacquin V, Kaloustian E, Larger E, Lecleire-Collet A, Lorenzini F, Louis J, Mausset J, Murat A, Nadler-Fluteau S, Olivier F, Paquis-Flucklinger, V., Paris-Bockel D, Raynaud I, Reznik Y, Riveline JP, Schneebeli S, Sonnet E, Sola-Gazagnes A, Thomas JL, Trabulsi B, Virally M, Guillausseau PJ; Mitochondrial Diabetes French Study Group. The clinical variability of maternally inherited diabetes and deafness is associated with the degree of heteroplasmy in blood leukocytes. J Clin Endocrinol Metab, 94:3025-30 (2009).

    2008


    • Bannwarth S, Procaccio V, Rouzier C, Fragaki K, Poole J, Chabrol B, Desnuelle C, Pouget J, Azulay JP, Attarian S, Pellissier JF, Gargus JJ, Abdenur JE, Mozaffar T, Calvas P, Labauge P, Pages M, Wallace DC, Lambert JC, Paquis-Flucklinger, V. Rapid identification of mitochondrial DNA (mtDNA) mutations in neuromuscular disorders by using surveyor strategy. Mitochondrion, 8:136-45 (2008)

    • Plantiga RF, Pennings RJ, Huygen PL, Bruno R, Heller P, Barrett TG, Vialettes B, Paquis-Flucklinger, V., Lombardo F, Cremers W. Hearing impairment in genotyped Wolfram syndrome patients. Ann Otol Rhinol Laryngol, 117 : 497-500 (2008)

    • Massin P, Dubois-Laforgue D, Meas T, Laloi-Michelin M, Gin H, Bauduceau B, Bellanné-Chantelot C, Bertin E, Blickle JF, Bouhanick B, Cahen-Varsaux J, Casanova S, Charpentier G, Chedin P, Dupuy O, Grimaldi A, Guerci B, Kaloustian E, Lecleire-Collet A, Lorenzini F, Murat A, Narbonne H, Olivier F, Paquis-Flucklinger, V., Virally M, Vincenot M, Vialettes B, Timsit J, Guillausseau PJ; for the GEDIAM (Mitochondrial Diabetes French Study Group). Retinal and renal complications in patients with a mutation of mitochondrial DNA at position 3,243 (maternally inherited diabetes and deafness). A case-control study. Diabetologia, 51:1664-1670 (2008).

    • Valéro R, Bannwarth S, Roman S, Paquis-Flucklinger, V., Vialettes B. Autosomal dominant transmission of diabetes and congenital hearing impairment secondary to a missense mutation in the WFS1 gene. Diabet Med, 25:657-61 (2008).

    2007


    • Neyton S, Lespinasse F, Lahaye F, Staccini P, Paquis-Flucklinger, V., Santucci-Darmanin S. CRM1-dependent nuclear export and dimerization with hMSH5 contribute to the regulation of hMSH4 subcellular localization. Exp Cell Res, 313: 3680-93 (2007).

    • Bourdon A, Minai L, Serre V, Jais JP, Sarzi E, Aubert S, Chrétien D, de Lonlay P, Paquis-Flucklinger, V., Arakawa H, Nakamura Y, Munnich A, Rôtig A. Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nat Genet, 39 : 776-780 (2007).

    • Cano A, Molines L, Valéro R, Simonin G, Paquis-Flucklinger, V., Vialettes B; French Group of Wolfram Syndrome. Microvascular diabetes complications in Wolfram syndrome (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness [DIDMOAD]): an age- and duration-matched comparison with common type 1 diabetes. Diabetes Care, 30 : 2327-30 (2007).

    • Cano A, Rouzier C, Monnot S, Chabrol B, Conrath J, Lecomte P, Delobel B, Boileau P, Valero R, Procaccio V, Paquis-Flucklinger, V.; French Group of Wolfram Syndrome, Vialettes B. Identification of novel mutations in WFS1 and genotype-phenotype correlation in Wolfram syndrome. Am J Med Genet A, 143A(14):1605-12 (2007).

    2006


    • Bannwarth S, Procaccio V, Paquis-Flucklinger, V. Rapid identification of unknown heteroplasmic mutations across the entire human mitochondrial genome with mismatch-specific Surveyor Nuclease. Nat Protoc, 4: 2037-2047 (2006)

    • Naïmi M, Bannwarth S, Procaccio V, Pouget J, Desnuelle C, Pellissier JF, Rötig A, Munnich A, Calvas P, Richelme C, Jonveaux P, Castelnovo G, Simon M, Clanet M, Wallace D, Paquis-Flucklinger, V. Molecular analysis of ANT1, Twinkle and POLG in patients with multiple deletions or depletion of mitochondrial DNA by a dHPLC-based assay. Eur J Hum Genet, 14, 917-922 (2006).

    • Bouchet C, Steffan J, Corcos J, Monnot S, Paquis-Flucklinger, V., Rotig A, Lebon S, Levy P, Royer G, Giurgea I, Gigarel N, Benachi A, Dumez Y, Munnich A, Bonnefond JP. Prenatal diagnosis of MELAS syndrome : contribution to understanding mitochondrial DNA segregation during human embryo fœtal development. J Med Genet. 11 (2006).

    • Procaccio V, Neckelmann N, Paquis-Flucklinger, V., Bannwarth S., Jimenez R, Davila A, Poole JC, Wallace DC. Detection of low levels of the 3243A>G mutation in mitochondrial DNA in blood derived from diabetic patients. Mol Diagnosis Therapy, 10 : 381-389 (2006).


    Financial Grants

    Financial Grants





    logo-chu-2014