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Osservatorio sulle Connettivopatie Ereditarie (OCE)

Prof.ssa Colombi Marina (DMMT)
Prof.ssa Zoppi Nicoletta (DMMT)
Dott. Ritelli Marco, Ricercatore (DMMT)
Dott. Chiarelli Nicola, Borsista (DMMT)
Dott.ssa Valeria Cinquina, assegnista (DMMT).
Prof. Calzavara Pinton Piergiacomo (DSCS)
Prof.ssa Venturini Marina (DSCS)

Le Connettivopatie ereditarie, o disordini ereditari del tessuto connettivo, sono un ampio gruppo di sindromi geneticamente determinate, che clinicamente presentano il coinvolgimento di più organi e apparati costituiti prevalentemente da tessuto connettivo, in particolar modo gli apparati cutaneo, cardiovascolare, articolare, oculare e osseo. Mutazioni in geni, che codificano per proteine strutturali, per proteoglicani e per enzimi e fattori di crescita che regolano la loro maturazione e sintesi, sono responsabili di alcune centinaia di disordini specifici.

La maggior parte di queste malattie si trasmette con modalità autosomica dominante, ma anche la trasmissione autosomica recessiva è presente nei casi in cui siano colpiti geni che codificano per enzimi e/o fattori di trascrizione/crescita, o per proteine con effetto regolativo e non strutturale.

Data la rarità di queste malattie genetiche vi sono pochi specialisti che si occupano attualmente della loro definizione clinica e molecolare sia in Italia che all’estero.

L’OCE persegue le seguenti finalità:

- Sviluppare le conoscenze sulle connettivopatie ereditarie a prevalente coinvolgimento cutaneo, muscoloscheletrico e vascolare, sia dal punto di vista clinico che molecolare.
- Definire approcci clinici e molecolari sempre più specifici per la diagnosi delle connettivopatie ereditarie rare e ulta-rare.
- Definire le basi genetiche della sindrome di Ehlers-Danlos ipermobile e dei fenotipi relati mediante approcci omici.
- Indagare i meccanismi patogenetici delle connettivopatie ereditarie in previsione di approcci terapeutici mirati.
- Definire linee guida aggiornate ed efficaci per una diagnosi sempre più precoce e per un supporto multidisciplinare adeguato per i pazienti affetti da connettivopatie ereditarie.
- Promuovere la preparazione del registro italiano dei pazienti affetti da sindromi di Ehlers-Danlos in collaborazione con i centri diagnostici e gli specialisti che operano sul territorio nazionale.
- Promuovere la diffusione delle conoscenze sulle connettivopatie ereditarie, a livello locale, nazionale e internazionale tra gli specialisti, le associazioni dei malati e i malati.

L’attività dell’Osservatorio è stata supportata dai seguenti finanziamenti:

2013-’15: Fondazione Telethon, progetto finanziato: “Arterial Tortuosity Syndrome: a vitamin C compartmentation disease?” (Grant GGP13167) Responsabile Scientifico: Prof.ssa M. Colombi

2016-’18: Bando di Ateneo Health & Wealth 2015, progetto finanziato “Sviluppo di una piattaforma NGS e di pannelli genici per il miglioramento della diagnosi, della salute e del benessere di pazienti affetti da connettivopatie ereditarie e altre malattie mendeliane (SPEED-GENE)” (Start Grant) Responsabile scientifico: Prof.ssa M. Colombi

2017-‘18: Donazione liberale dell’Onlus CEDI, Clinici Ehlers-Danlos Italia.

1/5/2019: Ehlers-Danlos syndrome Society, $200K Grant No. #2018.02 Project entitled "Proteome profiling for hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders to unravel pathogenetic mechanisms and identify potential biomarkers supporting clinical diagnosis". Principal Investigator: Prof Marina Colombi, https://www.ehlers-danlos.com/funded-research/

28/10/2019: Ehlers-Danlos syndrome Society, Grant Number: 2019.01.RFP.01, Project entitled: RNA sequencing to define pathogenetic mechanisms involved in hypermobile Ehlers-Danlos syndrome and Hypermobility Spectrum Disorders. Principal Investigator: Prof. Marina Colombi.

Lavori pubblicati dal 2011 su riviste internazionali

1 Chiarelli N, Ritelli M, Zoppi N, Benini A, Borsani B, Barlati S, Colombi M. Characterization and expression pattern analysis of the facilitative glucose transporter 10 gene (slc2a10) in Danio rerio. 2011 Int J Dev Biol 55:229-36

2 Burkitt Wright EMM, Spencer HL, Daly SB, Manson FDC, Zeef LAH, Urquhart J, Zoppi N, Bonshek R, Tosounidis I, Mohan M, Madden C, Dodds A, Chandler KE, Banka S, Au L, Clayton-Smith J, Khan N, Biesecker LG, Wilson M, Rohrbach M, Colombi M, Giunta C, Black GCM. Mutations in PRDM5 in brittle cornea syndrome identify a novel pathway regulating extracellular matrix development and maintenance. 2011 Am J Hum Genet 88:767-77

3 Drera B, Zoppi N, Ritelli M, Tadini G, Venturini M, Wischmeijer A, Nicolazzi MA, Musumeci A, Penco S, Buscemi L, Crivelli S, Danesino C, Clementi M, Calzavara-Pinton PG, Viglio S, Valli M, Barlati S, Colombi M. Diagnosis of vascular Ehlers-Danlos syndrome in Italy: clinical findings and novel COL3A1 mutations. 2011 J Dermatol Sci, 64:237-240

4 Buscemi L, Alessandrini F, Colombi M, Tagliabracci A. Molecular autopsy in traumatic death. A case report. 2011 Forensic Sci Int Genetics Suppl, Series 3 (1) pp e220-221

5 Del Zotto E, Ritelli M, Pezzini A, Drera B, Gamba M, Giossi A, Volonghi I, Costa P, Barlati S, Gasparotti R, Padovani A, Colombi M. Carotid rete mirabile in a patient with pseudoxhantoma elasticum: clinical, neuroradiological and molecular characterization. 2012 Clin Neurol Neurosurg, 114(6):758-61

6 Baumann M, Giunta C, Krabichler B, Rüschendorf F, Zoppi N, Colombi M, Bittner RE, Quijano-Roy S, Muntoni F, Cirak S, Schreiber G, Hu YZY, Romero NB, Carlier RY, Amberger A, Deutschmann A, Straub V, Rohrbach M, Steinmann B, Rostásy K, Karall D, Bönnemann CG, Zschocke J, Fauth C. Mutations in FKBP14 cause a variant of Ehlers-Danlos syndrome with progressive kyphoscoliosis, myopathy, and hearing loss. 2012 Am J Hum Genet 90:201-16

7 Castori M, Ritelli M, Zoppi N, Chiarelli N, Molisso L, Zaccagna F,  Grammatico P, Colombi M. Adult presentation of arterial tortuosity syndrome in a 51-year-old woman with the novel homozygous c.1411+1G>A mutation in the SLC2A10 gene. 2012 Am J Med Genet 158A:1164-9

8 Fattori R, Sangiorgio P, Mariucci E, Ritelli M, Wischmeijer A, Greco C, Colombi M. Spontaneous coronary artery dissection in a young woman with Loeys-Dietz syndrome. 2012 Am J Med Genet, 158A:1216-8

9 Castori M, Morlino S., Celletti C, Celli M, Morrone A, Colombi M, Camerota F, Grammatico P. Management of pain and fatigue in the joint hypermobility syndrome (Ehlers-Danlos syndrome, hypermobility type): principles and proposal for a multidisciplinary approach. 2012 Am J Med Genet 158A:2055-70

10 Castori M, Morlino S, Dordoni C, Celletti C, Camerota F, Ritelli M, Venturini M, Grammatico P, Colombi M. Gynecologic and obstetric implications of the joint hypermobility syndrome (a.k.a. Ehlers-Danlos syndrome hypermobility type) in 82 Italian women. 2012 Am J Med Genet 158A:2176-82

11 Zoppi N, Ritelli M, Colombi M. Type III and V collagens modulate the expression and assembly of EDA+ fibronectin in the extracellular matrix detective Ehlers-Danlos syndrome skin fibroblasts. 2012 Biochim Biophys Acta, 1820:1576-1587

12 Ritelli M, Chiarelli N, Quinzani S, Dordoni C, Venturini M, Calzavara-Pinton P, Colombi M. Compound heterozygosity of the novel -186C>T mutation in the COL7A1 promoter and the recurrent c.497insA mutation leads to generalised dystrophic epidermolysis bullosa. 2013 Br J Dermatol, 168:904-906

13 Pezzini A, Grassi M, Del Zotto E, Giossi A, Volonghi I, Costa P, Poli L, Gamba M, Ritelli M, Colombi M, Padovani A. Complications of acute stroke and the occurrence of early seizures. 2013 Cerebrovascular Diseases, 35(5):444-50

14 Wischmeijer A, Van Laer L, Tortora G, Bolar NA, Van Camp G, Fransen E, di Bartolomeo R, Pacini D, Gargiulo G, Turci S, Bonvicini M, Mariucci E, Lovato L, Brusori S, Ritelli M, Colombi M, Garavelli L, Seri M, Loeys BL. First report of thoracic aortic aneurysm in infancy in a family with aneurysms-osteoarthritis syndrome due to a novel SMAD3 mutation: further delineation of the clinical phenotype. 2013 Am J Med Genet, 161(5):1028-35

15 Ritelli M, Venturini M, Dordoni C, Chiarelli N, Quinzani S, Traversa M, Zoppi N, Vascellaro A, Wischmeijer A, Manfredini E, Garavelli L, Calzavara-Pinton P, Colombi M. Clinical and molecular characterization of 40 patients with classic Ehlers-Danlos syndrome: identification of 18 COL5A1 and 2 COL5A2 novel mutations. 2013 Orphanet J Rare Dis, Apr 12;8:58, 13 pp

16 Dordoni C, Ritelli M, Venturini M, Chiarelli N, Pezzani L, Vascellaro A, Calzavara-Pinton P, Colombi M. Recurring and generalized visceroptosis in Ehlers-Danlos syndrome hypermobility type. 2013 Am J Med Genet, 161(5):1143-7

17 Pezzani L, Brena M, Callea M, Colombi M, Tadini G. X-linked Reticulate Pigmentary Disorder with systemic manifestations: a new family and review of the literature. 2013 Am J Med Genet, 161A(6):1414-1420

18 Castori M, Morlino S, Ritelli M, Brancati F, De Bernardo L, Colombi M, Grammatico P. Late diagnosis of lateral meningocele syndrome in a 55-year-old woman with joint instability complications and chronic musculoskeletal pain. 2014 Am J Med Genet, 164A(2):528-34

19 Pezzini A, Grassi M, Paciaroni M, Zini A, Silvestrelli G, Del Zotto E, Caso V, Frigio Nichelli P, Giossi A, Volonghi I, Anna Maria, Simone, Lanari A, Costa P, Poli L, Morotti A, De Giuli V, Pepe D, Gamba M, Ciccone A, Ritelli M, Colombi M, Agnelli G, Padovani A. Antithrombotic medications and the etiology of intracerebral hemorrhage. The MUCH-Italy. 2014 Neurology, Feb 11;82(6):529-35

20 Ritelli M, Chiarelli N, Dordoni C, Quinzani S, Pezzani L, Venturini M, Calzavara-Pinton P, Colombi M. Identification of two novel ATP6V0A2 mutations in an infant with cutis laxa by exome sequencing. 2014 J Dermatol Sci, 75:66-68

21 Ritelli M, Chiarelli N, Dordoni C, Venturini M, Maroldi R, Calzavara-Pinton P, Colombi M. Further delineation of Loeys-Dietz syndrome type 4 in a family with mild vascular involvement and a TGFB2 splicing mutation. 2014 BMC Med Genet 15:91

22 Ritelli M, Chiarelli N, Dordoni C, Venturini M, Quinzani S, Della Monica M, Reffo E, Scarano G, Calzavara-Pinton P, Milanesi O, Colombi M. Arterial Tortuosity Syndrome: homozygosity for two novel and one recurrent SLC2A10 missense mutations in three families with severe cardiopulmonary complications in infancy and a literature review. 2014 BMC Med Genet 15:122

23 Castori M, Dordoni C, Valiante M, Sperduti I, Ritelli M, Morlino S, Chiarelli N, Celletti C, Venturini M, Calzavara-Pinton P, Camerota F, Grammatico P, Colombi M. Nosology, and Inheritance pattern (s) of Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome, Hypermobility Type: A Study of Intrafamilial and Interfamilial Variability in 23 Pedigrees. 2014 Am J Med Genet, 164A:3010-20

24 Giossi A, Ritelli M, Costa P, Morotti A, Poli, Del Zotto E, Volonghi I, Chiarelli N, Gamba M, Bovi P, Tomelleri G, Carletti M, Checcarelli N, Meneghetti G, Morra M, Chinaglia M, De Giuli V, Colombi M, Padovani A, Pezzini A. Connective tissue anomalies in patients with spontaneous cervical artery dissection. 2014 Neurology 25:2032-7

25 Castori M, Dordoni C, Morlino S, Sperduti I, Ritelli M, Valiante M, Chiarelli N, Zanca A, Celletti C, Venturini M, Camerota F, Calzavara-Pinton P, Grammatico P, Colombi M. Spectrum of mucocutaneous manifestations in 277 patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. 2015 Am J Med Genet part C “Generalized Joint Hypermobility, Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome, Hypermobility Type: Emerging Issues and Future Perspectives”. 169:43-53

26 Ritelli M, Chiarelli N, Zoppi N, Dordoni C, Quinzani S, Traversa M, Venturini M, Calzavara-Pinton M, Colombi M. Insights in the etiopathology of galactosyltransferase II (GalT-II) deficiency from transcriptome-wide expression profiling of skin fibroblasts of two sisters with compound heterozygosity for two novel B3GALT6 mutations. 2015 Mol Gen Metab Rep 2:1-15

27 Pieroni A, Castori M, Caso P, Di Bernardini E, De Michele M, Ritelli M, Colombi M, Toni D. Aortic dissection and stroke in a 37-year-old woman: discovering an emerging heritable connective tissue disorder. 2015 Internal and Emergency Medicine, 10:165-170

28 Parisi R, Cocco G, Ritelli M, Marinucci L, Secco GG, Uguccioni L, Colombi M, Goffi L, Fattori R. Aortic rupture after thoracic endovascular repair in a patient with familial thoracic aortic aneurysm and dissections type 6 (FTAAD6). 2016 J Cardiovasc Surg (Torino), Jul 27. 57(3):482-3

29 Colombi M, Dordoni C, Chiarelli N, Ritelli M. Differential diagnosis and diagnostic flow chart of Joint Hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type compared to other heritable connective tissue disorders. 2015 Am J Med Genet part C “Generalized Joint Hypermobility, Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome, Hypermobility Type: Emerging Issues and Future Perspectives”. 169:6-22

30 Castori M, Colombi M. Introduction to “Generalized Joint Hypermobility, Joint Hypermobility Syndrome and Ehlers-Danlos Syndrome, Hypermobility Type: Emerging Issues and Future Perspectives”. 2015 Am J Med Genet part C 169:1-5

31 Porter LF, Gallego-Pinazo R, Keeling C, Kamieniorz M, Zoppi N, Colombi M, Giunta C, Bonshek R, Manson F, Black G. Bruch's membrane abnormalities in PRDM5-related brittle cornea syndrome. 2015 Orphanet J Rare Diseases 10:145

32 Zoppi N, Chiarelli N, Cinquina V, Ritelli M, Colombi M. GLUT10 deficiency leads to oxidative stress and non-canonical αvβ3 integrin-mediated TGFβ signalling associated with extracellular matrix disarray in arterial tortuosity syndrome skin fibroblasts 2015 Hum Molec Genet, 24:6769-87

33 Mazziotti G, Dordoni C, Doga M, Galderisi F, Venturini M, Calzavara-Pinton P, Maroldi R, Giustina A, Colombi M. High prevalence of radiological vertebral fractures in adult patients with Ehlers-Danlos syndrome. 2016 Bone 84:88-92

34 Castori M, Colombi M. From the bedside to the bench and backwards: diagnostic approach and management of Ehlers-Danlos syndrome(s) in Italy. 2016 Journal de Réadaptation Médicale, JRM-350 No of Pages 19

35 Németh CE, Marcolongo P, Gamberucci A, Fulceri R, Benedetti A, Zoppi N, Ritelli M, Chiarelli N, Colombi M, Willaert A, Callewaert BL, Coucke PJ, Gróf P, Nagy SK, Mészáros T, Bánhegyi G, Margittai É. GLUT10 - lacking in arterial tortuosity syndrome - facilitates dehydroascorbic acid transport. 2016 FEBS Lett 590(11):1630-40

36 Cotlarciuc I, Marjot T, Khan MS, Hiltunen S, Haapaniemi E, Metso TM, Putaala J, Zuurbier SM, Brouwer MC, Passamonti SM, Bucciarelli P, Pappalardo E, Patel T, Costa P, Colombi M, Canhão P, Tkach A, Santacroce R, Margaglione M, Favuzzi G, Grandone E, Colaizzo D, Spengos K, Arauz A, Hodge A, Ditta R, Debette S, Zedde M, Pare G, Ferro JM, Thijs V, Pezzini A, Majersik JJ, Martinelli I, Coutinho JM, Tatlisumak T, Sharma P; ISGC (International Stroke Genetics Consortium) and BEAST investigators. Towards the genetic basis of cerebral venous thrombosis-the BEAST Consortium: a study protocol. 2016 BMJ Open. Nov 22;6(11):e012351

37 Dordoni C, Ciaccio C, Venturini M, Calzavara-Pinton P, Ritelli M, Colombi M. Further delineation of FKBP14-related Ehlers-Danlos syndrome: a patient with early vascular complications and non-progressive kyphoscoliosis, and literature review. 2016 Am J Med Genet 170:2031-38

38 Cazzato D, Castori M, Lombardi R, Caravello F, Bella ED, Petrucci A, Grammatico P, Dordoni C, Colombi M, Lauria G. Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes. 2016 Neurology 87:155-59

39 Chiarelli N, Carini G, Zoppi N, Dordoni C, Ritelli M, Venturini M, Castori M, Colombi M. Transcriptome-wide expression profiling in skin fibroblasts of patients with Joint Hypermobility Syndrome/Ehlers-Danlos syndrome hypermobility type. 2016 PLOSone, Aug 12;11(8):e0161347

40 Ciaccio C, Dordoni C, Colombi M. 17q21.31 microdeletion syndrome: report of an adult presentation. 2016 Cytogenet Genome Res 150(1):40-45

41 Dordoni C, Ciaccio C, Santoro G, Venturini M, Cavallari U, Ritelli M, Colombi M. Marfan syndrome: report of a complex phenotype due to a 15q21.1 gene deletion encompassing FBN1, and literature review. 2017 Am J Med Genet A Jan;173(1):200-206

42 Martinelli-Boneschi F, Colombi M, Castori M, Devigili G, Eleopra R, Malik RA, Ritelli M, Zoppi N, Dordoni C, Sorosina M, Grammatico P, Fadavi H, Gerrits MM, Almomani R, Faber CG, Merkies IS, Toniolo D, Cocca M, Doglioni C, Waxman SG, Dib-Hajj SD, Taiana MM, Sassone J, Lombardi R, Cazzato D, Zauli A, Santoro S, Marchi M, Lauria G; INGI Network. COL6A5 variants cause familial chronic itch. 2017 Brain Mar 1;140(3):555-567

43 Ritelli M, Morlino S, Giacopuzzi E, Carini G, Cinquina V, Chiarelli N, Majore S, Colombi M, Castori M. Ehlers-Danlos syndrome with lethal cardiac valvular dystrophy in males carrying a novel splice mutation in FLNA. 2017 Am J Med Genet A Jan;173(1):169-17

44 Giossi A, Mardighian D, Caria F, Costa P, Morotti A, Poli L, De Giuli V, Gamba M, Ritelli M, Colombi M, Sessa M, Grassi M, Padovani A, Gasparotti R, Pezzini A. Arterial Tortuosity in Patients with Spontaneous Cervical Artery Dissection. 2017 Neuroradiol 59(6):571-575

45 Colombi M, Dordoni C, Venturini M, Zanca A, Calzavara-Pinton P, Ritelli M. Delineation of Ehlers-Danlos syndrome phenotype due to the c.934C>T (p.Arg312Cys) mutation in COL1A1: report on a three generation family without cardiovascular events and literature review. 2017 Am J Med Genet part A 173(2):524-530

46 Morlino S, Dordoni C, Sperduti I, Venturini M, Celletti C, Camerota F, Grammatico P, Colombi M, Castori M. Refining patterns of joint hypermobility, habitus and orthopedic traits in joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type. 2017 Am J Med Genet part A 173(4):914-929

47 Ritelli M, Palit A, Giocopuzzi E, Inamadar AC, Dordoni C, Mujja A, Murgude MS, Colombi M. Clinical and molecular characterization of a 13-year-old Indian boy with cutis laxa type 2B: identification of two novel PYCR1 mutations by amplicon-based semiconductor exome sequencing. 2017 J Dermatol Sci Apr 29. pii: S0923-1811(16)30736-8

48 Gamberucci A, Marcolongo P, Németh CE, Zoppi N, Szarka A, Chiarelli N, Hegedűs T, Ritelli M, Carini G, Willaert A, Callewaert BL, Coucke PJ, Benedetti A, Margittai É, Fulceri R, Bánhegyi G, Colombi M. GLUT10 - lacking in arterial tortuosity syndrome – is localized to the endoplasmic reticulum and nuclear envelope. 2017 Int J Mol Sci 18, 1820

49 Ritelli M, Morlino S, Giacopuzzi E, Bernardini L, Torres B, Santoro G, Ravasio V, Novelli A, Grammatico P, Colombi M, Castori M. A recognizable systemic connective tissue disorder with polyvalvular heart dystrophy and dysmorphism associated with TAB2 mutations. 2018 Clin Genet, Jan;93(1):126-133.

50 Colombi M, Dordoni C, Venturini M, Ciaccio C, Morlino S, Chiarelli N, Zanca A, Calzavara-Pinton P, Zoppi N, Castori M, Ritelli M. Spectrum of mucocutaneous, ocular and facial features and delineation of novel presentations in 62 classical Ehlers-Danlos syndrome patients. 2017 Clin Genet Dec;92(6):624-631

51 Bowen JM, SoDec;92(6):624-631bey GJ, Burrows NP, Colombi M, Lavallee ME, Malfait F, Francomano CA. Ehlers-Danlos syndrome, classical type. Am J Med Genet C 2017 Mar;175(1):27-39. Review.

52 Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, Bloom L, Bowen JM, Brady AF, Burrows NP, Castori M, Cohen H, Colombi M, Demirdas S, De Backer J, De Paepe A, Fournel-Gigleux S, Frank M, Ghali N, Giunta C, Grahame R, Hakim A, Jeunemaitre X, Johnson D, Juul-Kristensen B, Kapferer-Seebacher I, Kazkaz H, Kosho T, Lavallee ME, Levy H, Mendoza-Londono R, Pepin M, Pope FM, Reinstein E, Robert L, Rohrbach M, Sanders L, Sobey GJ, Van Damme T, Vandersteen A, van Mourik C, Voermans N, Wheeldon N, Zschocke J, Tinkle B.The 2017 International Classification of the Ehlers-Danlos Syndromes. 2017 Am J Med Genet C Mar;175(1):8-26

53 Colombi M, Dordoni C, Cinquina V, Venturini M, Ritelli M. A classical Ehlers-Danlos syndrome family with incomplete presentation diagnosed by molecular testing. 2018 Eur J Med Genet Jan;61(1):17-20

54 Dordoni C, Gatti M, Venturini M, Zanca A, Cinquina V, Santoro G, Battocchio S, Calzavara-Pinton P, Ritelli M, Colombi M. Characterization of a Pxeudoxhantoma elasticum-like patient with coagulation deficiency, cutaneous calcinosis and GGCX compound heterozygosity. 2018 J Dermatol Sci Feb;89(2):201-204

55 Zoppi N, Chiarelli N, Binetti S, Ritelli M, Colombi M. Dermal fibroblast-to-myofibroblast transition as a common feature for hypermobile EDS and hypermobility spectrum disorders. 2018 Biochim Biopys Acta Molecular Basis of Diseases 1864(4 Pt A):1010-102

56 Ritelli M, Dordoni C, Cinquina V, Venturini M, Colombi M. Expanding the clinical and mutational spectrum of B4GALT7-spondylodysplastic Ehlers-Danlos syndrome. 2017 Orphanet J Rare Dis Sep 7;12(1):153

57 Chiarelli N, Carini G, Zoppi N, Ritelli M, Colombi M. Transcriptome analysis of skin fibroblasts with dominant negative COL3A1 mutations provides molecular insights into the etiopathology of vascular Ehlers-Danlos syndrome. 2018 PLOSOne, 13(1):e0191220.

58 Kocova M, Kacarska R, Kuzevska-Maneva K, Prijic S, Lazareska M, Dordoni C, Ritelli M, Colombi M. Clinical variability in two Macedonian families with arterial tortuosity syndrome. 2018, Balkan J Med Genet 21(1):47-52

59 Piedimonte C, Penge R, Morlino S, Sperduti I, Terzani A, Giannini MT, Colombi M, Grammatico P, Cardona F, Castori M. Exploring relationships between joint hypermobility and neurodevelopment in pediatric patients (4-13 years) with hereditary connective tissue disorders and developmental coordination disorder. 2018 Am J Med Genet B Neuropsychiatr Genet Sep;177(6):546-556

60 Zoppi N, Chiarelli N, Ritelli M, Colombi M. Multifaced roles of the αvß3 integrin in Ehlers-Danlos and Arterial Tortuosity syndromes. 2018 Int J Mol Sci Mar 26;19(4). pii: E982. Review

61 Morlino S, Castori M, Dordoni C, Cinquina V, Santoro G, Grammatico P, Venturini M, Colombi M, Ritelli M. A novel MAP3K7 splice mutation causes cardiospondylocarpofacial syndrome with features of hereditary connective tissue disorder. 2018 Eur J Hum Genet 26:582–586

62 Morlino S, Dordoni C, Sperduti I, Clark CJ, Piedimonte C, Fontana A, Colombi M, Grammatico P, Copetti M, Castori M. Italian validation of the functional difficulties questionnaire (FDQ-9) and its correlation with major determinants of quality of life in adults with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorder. 2019 Am J Med Genet B Neuropsychiatr Genet 180(1):25-34

63 Formenti AM, Doga M, Frara S, Ritelli M, Colombi M, Banfi G, Giustina A. Skeletal fragility: an emerging complication of Ehlers-Danlos syndrome. 2019 Endrocrine 63(2):225-230

64 Chiarelli N, Carini G, Zoppi N, Ritelli M, Colombi M. Molecular insights in the pathogenesis of classical Ehlers-Danlos syndrome from transcriptome-wide expression profiling of patients’ skin fibroblasts. 2019 PLOSone Feb 4;14(2):e0211647

65 Németh CE, Nemoda N, Lőw P, Szabó P, Horváth EZ, Willaert A, Boel A, Callewaert BL, Coucke PJ, Colombi M, Bánhegyi G, Margittai E. Decreased Nuclear Ascorbate Accumulation Accompanied with Altered Genomic Methylation Pattern in Fibroblasts from Arterial Tortuosity Syndrome Patients. 2019 Oxidative Medicine and Cellular Longevity 11 pages, Article ID 8156592

66 Laterza D, Ritelli M, Zini A, Colombi M, Dell’Acqua ML, Vandelli L, Bigliardi G, Verganti L, Vallone S, Vincenzi C, Rosafio F, Ciolli L, Calabrese O, Nichelli PF, Picchetto L. Two novel pathogenic variants in TGFBR1 and SMAD3 identified after cerebrovascular events in adult patients with Loeys-Dietz syndrome. 2019 Eur J Mol Genet Oct;62(10):103727

67 Chiarelli N, Ritelli M, Zoppi N, Colombi M. Cellular and molecular mechanisms in the pathogenesis of Hypermobile, classical, and vascular Ehlers-Danlos syndromes. 2019 Genes Aug 12;10(8). pii: E609. Review

68 Ritelli M, Cinquina V, Giacopuzzi E, Venturini M, Chiarelli N, Colombi M. Further defining the phenotypic spectrum of B3GAT3 mutations and literature review on linkeropathy syndromes. 2019 Genes(Basel) Aug 21;10(9). pii: E631

69 Morlino S, Carbone A, Ritelli M, Fusco C, Nardella G, Giambra V, Notarangelo A, Panelli P, Mazzoccoli G, Zoppi N, Grammatico P, Colombi M, Castori M, Micale L. TAB2 c.1398dup variant leads to haploinsufficiency and impairs extracellular matrix remodeling. 2019 Human Mut Oct;40(10):1886-1898

70 Copetti M, Morlino S, Colombi M, Grammatico P, Fontana A, Castori M. Severity classes in adults with hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders: a pilot study on 105 Italian patients. 2019 Rheumatology, (Oxford) 2019 Oct 1;58(10):1722-1730

71 Ritelli M, Rovati C, Venturini M, Chiarelli N, Cinquina V, Castori M, Colombi M. Application of the 2017 criteria for vascular Ehlers-Danlos syndrome in a cohort of 50 molecularly proven individuals previously ascertained according to the Villefranche nosology. 2019 Clin Genet Oct 10. doi: 10.1111/cge.13653. [Epub ahead of print]

72 Angwin C, Brady AF, Colombi M, Ferguson DJP, Pollitt R, Pope FM, Ritelli M, Symoens S, Ghali N, van Dijk FS. Absence of collagen flowers on electron microscopy and identification of (likely) pathogenic COL5A1 variants in two patients. 2019 Genes (Basel) Sep 27;10(10). pii: E762

73 Camerota L, Ritelli M, Wischmeijer A, Majore S, Cinquina V, Fortugno P, Monetta R, Gigante L, Hospital MSSGTVU, Sangiuolo FC, Novelli G, Colombi M, Brancati F. Genotypic categorization of Loeys-Dietz syndrome based on 24 novel families and literature data. Genes (Basel). 2019 Sep 28;10(10). pii: E764

74 Rymen D, Ritelli M, Zoppi N, Cinquina V, Giunta C, Rohrbach M, Colombi M. Clinical and molecular characterization of classical-like Ehlers-Danlos syndrome due to a novel pathogenic TNXB variant. 2019 Genes (Basel) Oct 25;10(11). pii: E843

75. Li J, Ritelli M, Ma CS, Rao G, Habib T, Corvilain E, Bougarn S, Cypowyj S, Grodecká L, Lévy R, Béziat V, Shang L, Payne K, Avery DT, Migaud M, Boucherit S, Boughorbel S, Guennoun A, Chrabieh M, Rapaport F, Bigio B, Itan Y, Boisson B, Cormier-Daire V, Syx D, Malfait F, Zoppi N, Abel L, Freiberger T, Dietz HC, Marr N, Tangye SG, Colombi M, Casanova JL, Puel A. Chronic mucocutaneous candidiasis and connective tissue disorder in humans with impaired JNK1-dependent responses to IL-17A/F and TGF-β. Sci Immunol. 2019 Nov 29;4(41). pii: eaax7965.