Aller à la navigation Aller à la recherche

Link to the website



Important News

  • 28th May 2015 : EURORDIS Membership meeting 2015 at Madrid
  • 21th April 2015 : First tests over, major updates
  • 4th February 2015 : Beginning of Beta-Testing
  • 12th December 2014 : Meeting with RaDiCo about legal documents
  • 19th September 2014 : First meeting with RaDiCo team
  • 2nd September 2014 : Security and organisation meeting
  • 15th July 2014 : Official support of the RaDiCo program
  • 7th July 2014 : Project supported by the Xtraodinaire association, for beta-testing
  • 2nd June 2014 : Beginning of the development of the GenIDA website (by T. Mazzucotelli)
  • 29th May 2014 : Submission of the GenIDA project to the RaDiCo program


Santé 4P - GenIDA - Genetics - Intellectual Disability - Autism Spectrum Disorder - Social Network - Patient Empowerment


GenIDA : Genetics of Intellectual Disabilities & Autism

Intellectual disability (ID) is a mental disorder that constitutes a major health and social problem, which has been comparatively neglected until recently in medical research. It affects 1-2% of the population and shows a large overlap with autism. A genetic cause may be implicated in a majority of patients. ID is characterized by an extreme genetic heterogeneity that underlies a phenotypic heterogeneity in severity and in associated medical problems, with causes that can be chromosomal, notably including recurrent Copy Number Variants (CNVs), or single gene mutations. Progress in genome analysis has allowed the identification of more than 300-400 genes associated to monogenic forms of ID/autism, that can be associated or not to other medically significant manifestations. Each of these recurrent CNVs or mutated genes corresponds thus to a unique form of rare disease. Thanks to the striking technical progresses in genome analysis (CGH array, and now high-throughput sequencing), an increased number of genetic diagnoses are made in individuals with ID. Although this is useful for genetic counselling, the extraordinary genetic heterogeneity of ID will render extremely difficult the determination, for each specific cause (recurrent CNV or mutated gene), of genotype-phenotype correlations and natural history, the estimation of penetrance and variability of clinical expression. Symptomatic treatments for co-morbidities such as attention deficit, aggressive behavior or epilepsy will be proposed, with limited opportunities to assess their efficacies or potential serious adverse effects that may depend on the specific genetic cause of ID. And if for a given gene the specific pathomechanisms involved suggest a therapeutic strategy using an available drug, it will be very difficult to recruit enough patients sharing a defect in the same gene for a clinical trial, except for the most common causes. While the need for clinical databases allowing longitudinal follow-ups is well recognized, it is difficult to motivate physicians and costly to establish and maintain the large number of individual databases that would be required for such studies, and longitudinal information is often not available. We wish to develop an alternative database model for specific genetic causes of ID, organized in a social network format, whereby most clinical information would be entered by the family of the patient, based on wide range questionnaires established by professionals, but understandable by lay persons (and translated in several languages, to allow international participation). In particular we wish to gain relevant information for individualized medical care on risk of developing specific pathological complications and of possible serious adverse events linked to symptomatic medications. Recent examples show that medical information entered by patients can be the basis of useful research. Contacts between families affected by the same genetic cause could then be established in an initially anonymous way, creating gene or CNV specific social-networks to which interested professionals could be associated, akin to disease specific patients associations. Anonymized data could be accessible to professionals for specific projects approved by a comity composed of health or research professionals, of representatives of families or patients associations and of bioethicists. Concerned families could then decide to take part or not in such projects, and would also be informed of prospective clinical trials specific for the cognate gene. This proposal is based on the prior identification in a patient of causal mutations or highly penetrant CNV, and does not apply to individuals for whom the cause of ID is unknown or may result from oligogenic or multifactorial inheritances. The database could however be useful to recruit gene specific cohorts to estimate (from further familial segregation studies) the penetrance of mutations in a given gene.


Most relevant publications of the consortium

  1. C. Redin, B. Gérard, […], P. Sarda, P. Edery, B. Isidor, B. Jost, L. Olivier-Faivre, JL Mandel, A. Piton. Targeted High-Throughput Sequencing for the diagnosis of Intellectual Disability, submitted for publication (part of this work was selected for platform presentations at ASHG 2013, Boston and ESHG 2014, Milano)
  2. Piton A, Poquet H, Redin C, Masurel A, Lauer J, Muller J, Thevenon J, Herenger Y, Chancenotte S, Bonnet M, Pinoit JM, Huet F, Thauvin-Robinet C, Jaeger AS, Le Gras S, Jost B, Gérard B, Peoc'h K, Launay JM, Faivre L, Mandel JL. 20 ans après: a second mutation in MAOA identified by targeted high-throughput sequencing in a family with altered behavior and cognition. Eur J Hum Genet. 2013 Oct 30. doi: 10.1038/ejhg.2013.243.
  3. Piton A, Redin C, Mandel JL. XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing. Am J Hum Genet. 2013 Aug 8;93(2):368-83.
  4. Redin C, Le Gras S, Mhamdi O, Geoffroy V, Stoetzel C, Vincent MC, Chiurazzi P, Lacombe D, Ouertani I, Petit F, Till M, Verloes A, Jost B, Chaabouni HB, Dollfus H, Mandel JL, Muller J. Targeted high-throughput sequencing for diagnosis of genetically heterogeneous diseases: efficient mutation detection in Bardet-Biedl and Alström syndromes. J Med Genet. 2012 Aug;49(8):502-12.
  5. Subramanian M, Rage F, Tabet R, Flatter E, Mandel JL, Moine H. G-quadruplex RNA structure as a signal for neurite mRNA targeting. EMBO Rep. 2011 Jul 1;12(7):697-704.
  6. Cossée M, Faivre L, Philippe C, Hichri H, de Saint-Martin A, Laugel V, Bahi-Buisson N, Lemaitre JF, Leheup B, Delobel B, Demeer B, Poirier K, Biancalana V, Pinoit JM, Julia S, Chelly J, Devys D, Mandel JL. ARX polyalanine expansions are highly implicated in familial cases of mental retardation with infantile epilepsy and/or hand dystonia. Am J Med Genet A. 2011 Jan;155A(1):98-105.
  7. Stoetzel C, Muller J, Laurier V, Davis EE, […] Bonneau D, Katsanis N, Poch O, Mandel JL, Dollfus H. Identification of a novel BBS gene (BBS12) highlights the major role of a vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome. Am J Hum Genet. 2007 Jan;80(1):1-11.
  8. Stoetzel C, Laurier V, Davis EE, Muller J, […] Beales PL, Mandel JL, Katsanis N, Dollfus H. BBS10 encodes a vertebrate-specific chaperonin-like protein and is a major BBS locus. Nat Genet. 2006 May;38(5):521-4.
  9. Biancalana, V; Beldjord, C; Taillandier, A; Szpiro-Tapia, S; Cusin, V; Gerson, F; Philippe, C; Mandel, JL. French Natl Working Grp. 2004. Five years of molecular diagnosis of Fragile X syndrome(1997-2001): Acollaborative study reporting 95% of the activity in France. American J. Med. Genet. PART A 129A (3): 218-224.
  10. Schenck, A; Bardoni, B; Langmann, C; Harden, N; Mandel, JL; Giangrande, A. 2003. CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein. Neuron 38 (6): 887-898.
  11. Mandel JL, Chelly J. Monogenic X-linked mental retardation: is it as frequent as currently estimated? The paradox of the ARX (Aristaless X) mutations. Eur J Hum Genet. 2004 Sep;12(9):689-93.
  12. Chelly J, Mandel JL. Monogenic causes of X-linked mental retardation. Nat Rev Genet. 2001 Sep;2(9):669-80.
  13. A. Deruyver, Y. Hodé, L. Brun, Image Interpretation with a conceptual graph: labeling over-segmented images and detection of unexpected objects, Artificial Intelligence 173 (2009) 1245–1265.
  14. Yann Hodé, "Psychoéducation des patients et de leurs proches dans les épisodes psychotiques", L'Encéphale, Supplément 2 (2013) S110-S114. (Profamille)
  15. Yann Hodé, "Prise en charge des familles de patients schizophrènes", Annales Médico-Psychologiques 169 (2011) 196-199. (Profamille)
  16. Parrend, P. & Collet, P., Leveraging success factors of software projects: SCRUM is a complex system, ICCSA, 4th International Conference on Complex Systems and Applications, 2014
  17. Parrend, P.; Masai, P.; Zanni-Merk, C. & Collet, P., Swarm projects: beyond the metaphor, ICSIBO, International Conference on Swarm Intelligence Based Optimisation, 2014
  18. Legrand, V.; Parrend, P. & Gaouar, O., ArchiTrace : Apprentissage de la securite par les traces, WESSI - 1er Workshop sur l'Enseignement de la Securite des Systemes d'Information, 2014
  19. Goichon, F.; Salagnac, G.; Parrend, P. & Frénot, S., Static vulnerability detection in Java service-oriented components, Journal of Computer Virology and Hacking Techniques, Springer, 2013, 9, 15-26
  20. Colin F, Martelli A, Clémancey M, Latour JM, Gambarelli S, Zeppieri L, Birck C, Page A, Puccio H, Ollagnier de Choudens S. Mammalian frataxin controls sulfur production and iron entry during de novo Fe4S4 cluster assembly. J Am Chem Soc. 2013 Jan 16;135(2):733-40.

Selected bibliography

  1. Berry-Kravis, E.M., Hessl, D., Rathmell, B., Zarevics, P., Cherubini, M., Walton-Bowen, K., Mu, Y., Nguyen, D. V, Gonzalez-Heydrich, J., Wang, P.P., et al. (2012). Effects of STX209 (arbaclofen) on neurobehavioral function in children and adults with fragile X syndrome: a randomized, controlled, phase 2 trial. Sci. Transl. Med. 4, 152ra127.
  2. Do, C.B., Tung, J.Y., Dorfman, E., Kiefer, A.K., Drabant, E.M., Francke, U., Mountain, J.L., Goldman, S.M., Tanner, C.M., Langston, J.W., et al. (2011). Web-based genome-wide association study identifies two novel loci and a substantial genetic component for Parkinson’s disease. PLoS Genet. 7, e1002141.
  3. Ellison, J.W., Rosenfeld, J.A., and Shaffer, L.G. (2013). Genetic basis of intellectual disability. Annu. Rev. Med. 64, 441–450.
  4. Girirajan, S., Rosenfeld, J. a, Cooper, G.M., Antonacci, F., Siswara, P., Itsara, A., Vives, L., Walsh, T., McCarthy, S.E., Baker, C., et al. (2010). A recurrent 16p12.1 microdeletion supports a two-hit model for severe developmental delay. Nat. Genet. 42, 203–209.
  5. Goodman, M.J., and Brixner, D.I. (2013). New therapies for treating Down syndrome require quality of life measurement. Am. J. Med. Genet. A 161A, 639–641.
  6. Jacquemont, S., Hagerman, R.J., Leehey, M.A., Hall, D.A., Levine, R.A., Brunberg, J.A., Zhang, L., Jardini, T., Gane, L.W., Harris, S.W., et al. (2004). Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. JAMA 291, 460–469.
  7. Jacquemont, S., Curie, A., des Portes, V., Torrioli, M.G., Berry-Kravis, E., Hagerman, R.J., Ramos, F.J., Cornish, K., He, Y., Paulding, C., et al. (2011a). Epigenetic modification of the FMR1 gene in fragile X syndrome is associated with differential response to the mGluR5 antagonist AFQ056. Sci. Transl. Med. 3, 64ra1.
  8. Jacquemont, S., Reymond, A., Zufferey, F., Harewood, L., Walters, R.G., Kutalik, Z., Martinet, D., Shen, Y., Valsesia, A., Beckmann, N.D., et al. (2011b). Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus. Nature 478, 97–102.
  9. Johnson, K.J., Hussain, I., Williams, K., Santens, R., Mueller, N.L., and Gutmann, D.H. (2013). Development of an international internet-based neurofibromatosis Type 1 patient registry. Contemp. Clin. Trials 34, 305–311.
  10. Johnson, K.J., Mueller, N.L., Williams, K., and Gutmann, D.H. (2014). Evaluation of participant recruitment methods to a rare disease online registry. Am. J. Med. Genet. A.
  11. De la Torre, R., and Dierssen, M. (2012). Therapeutic approaches in the improvement of cognitive performance in Down syndrome: past, present, and future. Prog. Brain Res. 197, 1–14.
  12. Leblond, C.S., Heinrich, J., Delorme, R., Proepper, C., Betancur, C., Huguet, G., Konyukh, M., Chaste, P., Ey, E., Rastam, M., et al. (2012). Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders. PLoS Genet. 8, e1002521.
  13. De Ligt, J., Willemsen, M.H., van Bon, B.W.M., Kleefstra, T., Yntema, H.G., Kroes, T., Vulto-van Silfhout, A.T., Koolen, D. a, de Vries, P., Gilissen, C., et al. (2012). Diagnostic exome sequencing in persons with severe intellectual disability. N. Engl. J. Med. 367, 1921–1929.
  14. Rauch, A., Wieczorek, D., Graf, E., Wieland, T., Endele, S., Schwarzmayr, T., Albrecht, B., Bartholdi, D., Beygo, J., Di Donato, N., et al. (2012). Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet 380, 1674–1682.
  15. Schumacher, K.R., Stringer, K. a, Donohue, J.E., Yu, S., Shaver, A., Caruthers, R.L., Zikmund-Fisher, B.J., Fifer, C., Goldberg, C., and Russell, M.W. (2014). Social Media Methods for Studying Rare Diseases. Pediatrics.
  16. Tung, J.Y., Do, C.B., Hinds, D. a, Kiefer, A.K., Macpherson, J.M., Chowdry, A.B., Francke, U., Naughton, B.T., Mountain, J.L., Wojcicki, A., et al. (2011). Efficient replication of over 180 genetic associations with self-reported medical data. PLoS One 6, e23473.
  17. Wicks, P., Vaughan, T.E., Massagli, M.P., and Heywood, J. (2011). Accelerated clinical discovery using self-reported patient data collected online and a patient-matching algorithm. Nat. Biotechnol. 29, 411–414.
  18. Yang, Y., Muzny, D.M., Reid, J.G., Bainbridge, M.N., Willis, A., Ward, P. a, Braxton, A., Beuten, J., Xia, F., Niu, Z., et al. (2013). Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N. Engl. J. Med. 369, 1502–1511.