Pathophysiology of Pediatric Genetic Diseases
The research unit UMRS 933 INSERM/UPMC is devoted to the study of the pathophysiology of several human Mendelian disorders, including auto-inflammatory disorders and primary ciliary dyskinesia. We have access to cohorts of patients with these disorders, which are exceptional, both in their size and their phenotypic characterization. In spite of the identification, by our group, of several novel disease genes and a modifier gene, and functional studies concerning the corresponding proteins, the molecular and cellular bases of these disorders remain incompletely understood in the majority of these patients, justifying the search for new causative genes. Our research activities consist of a fundamental component and a translational aspect (coordination of 2 National Reference Centres for Rare Diseases —autoinflammatory syndromes and rare paediatric lung diseases — and participation in a third one on rare growth disorders; coordination of the national Rare Disease Cohorts (RaDiCo) program funded by the “Investissements d’Avenir”). For each pathology investigated, we develop on the top of the genetic profile (identification of new genetic factors involved the studied diseases) based on several complementary approaches, a functional profile with the design of disease-specific studies aimed at:
- developing disease-specific cell models,
- characterizing the molecular networks to which the proteins involved belong,
- evaluating, using different model systems, the consequences of the mutations identified in patients,
- and opening up new therapeutic avenues. The research conducted in our team leads to clinical implications with diagnostic, prognostic and therapeutic repercussions (translational research).
Fields of interest
Contact infoAddress: UMR_S933 INSERM/UPMC, Service de Génétique et d’Embryologie médicales, Hôpital Trousseau, 26 Avenue du Dr. Arnold Netter
Postal code: 75012
Telephone: + 33 1 44 73 52 95
Fax: +33 1 44 73 52 19
- Ratbi I, Fejjal N, Legendre M, Collot N, Amselem S, Sefiani A
Clinical and molecular findings in a Moroccan patient with popliteal pterygium syndrome: a case report
J Med Case Rep. 8, 471 (2014)
- Fritez N, Sobrier ML, Iraqi H, Vié-Luton MP, Netchine I, El Annas A, Pantel J, Collot N, Rose S, Piterboth W, Legendre M,Chraibi A, Amselem S, Kadiri A, Hilal L
Molecular screening of a large cohort of Moroccan patients with congenital hypopituitarism
Clin Endocrinol (Oxf) in press
- Jeanson L, Guerrera IC, Papon JF, Chhuon C, Zadigue P, Prulière-Escabasse V, Amselem S, Escudier E, Coste A, Edelman A
Proteomic analysis of nasal epithelial cells from cystic fibrosis patients
PLoS One 9(9), e108671 (2014)
- Jéru I, Cochet E, Duquesnoy P, Hentgen V, Copin B, Mitjavila-Garcia MT, Sheykholeslami S, Le Borgne G, Dastot-Le Moal F, Malan V, Karabina S, Mahevas M, Chantot-Bastaraud S, Lecron JC, Faivre L, Amselem S
Involvement of TNFRSF11A molecular defects in autoinflammatory disorders
Arthritis Rheumatol. 66(9), 2621-2627 (2014)
- Mory A, Dagan E, Shahor I, Mandel H, Illi B, Zolotushko J, Kurolap A, Chechik E, Valente EM, Amselem S, Gershoni-Baruch R
Kohlschutter-Tonz syndrome: clinical and genetic insights gained from 16 cases deriving from a close-knit village in Northern Israel
Pediatr Neurol. 50(4), 421-426 (2014)
- Grateau G, Hentgen V, Stojanovic KS, Jéru I, Amselem S, Steichen O.
How should we approach classification of autoinflammatory diseases ?
Nat Rev Rheumatol 2013; 9: 624-9
- Kott E, Legendre M, Copin B, Papon JF, Dastot-Le Moal F, Montantin G, Duquesnoy P, Piterboth W, Amram D, Bassinet L, Beucher J, Beydon N, Deneuville E, Houdouin V, Journel H, Just J et al.
Loss-of-function mutations in RSPH1 cause primary ciliary dyskinesia with central-complex and radial-spoke defects.
Am J Hum Genet. 2013 Sep 5;93(3):561-70.
- Jéru I, Hentgen V, Cochet E, Duquesnoy P, Le Borgne G, Grimprel E, Stojanovic KS, Karabina S, Grateau G, Amselem S.
The risk of familial Mediterranean fever in MEFV heterozygotes: a statistical approach.
PLoS One. 2013; 8: e68431
- Hentgen V, Grateau G, Stankovic-Stojanovic K, Amselem S, Jéru I.
Familial Mediterranean fever in heterozygotes: are we able to accurately diagnose the disease in very young children?
Arthritis Rheum. 2013, 65(6):1654-62.
- Kott E, Duquesnoy P., Copin B, Dastot-Le Moal F, Montantin G, Jeanson L, Tamamlet A, Papon JF, Rives N, Mitchell V, de Blic J, Coste A, Clement A, Escalier D, Touré A, Escudier E, Amselem S.
Loss-of-function mutations in LRRC6, a gene essential for propoer axonemal assembly of inner and outer dynein arms, cause primary ciliary dyskinesia.
Am. J. Hum. Genet., 2012,91(5):958-64
- Merveille AC, Davis EE, Becker-Heck A, Legendre M, … Clement A, Clercx C, Coste A, Crosbie R, de Blic J, Deleuze S, Duquesnoy P, Escalier D, Escudier E, … Georges M, Lequarré A, Katsanis N, Omran H, Amselem S.
CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs.
Nature Genet. 2011,43(1):72-8.