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Diagnosis of Primary Ciliary Dyskinesia (DCP)
This study is currently recruiting participants.
Verified August 2011 by Assistance Publique - Hôpitaux de Paris

First Received on October 31, 2008.   Last Updated on December 26, 2011   History of Changes
Sponsor: Assistance Publique - Hôpitaux de Paris
Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00783887
  Purpose

Primary ciliary dyskinesia is an inherited respiratory disease caused by various functional and ultrastructural abnormalities of respiratory cilia. The genetic heterogeneity underlying PCD is extremely important and only few genes are clearly implicated in PCD. Their mutations account for about 20% of patients. For all the other PCD patients, the genes responsible for their ciliary defect remain to be identify.


Condition Intervention
Primary Ciliary Dyskinesia
Kartagener Syndrome
 Other: Blood sample

Study Type: Observational
Study Design: Observational Model: Family-Based
Time Perspective: Cross-Sectional
Official Title: Molecular Diagnosis of Primary Ciliary Dyskinesia

Resource links provided by NLM:

Genetics Home Reference related topics: familial paroxysmal nonkinesigenic dyskinesia primary ciliary dyskinesia Help Me Understand Genetics
U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • After DNA extraction,standard procedures for the identification of human gene mutations will be used for each gene tested in the study [ Time Frame: At the inclusion visit ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complementary ciliary investigations in patients with suspected primary ciliary dyskinesia. [ Time Frame: At the inclusion visit ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA

DNA, Serum, White blood cells


Estimated Enrollment: 405
Study Start Date: January 2010
Estimated Study Completion Date: April 2013
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
Patients with suspected or confirmed primary ciliary dyskinesia after ciliary investigations who accepted to participate to the genetic studies
 Other: Blood sample
Blood sample of 5 ml
Other Name: Blood sample

Detailed Description:

1/ Evaluating the frequency of mutations of the two main genes implicated in PCD, in a large cohort of patients with PCD confirmed by ciliary investigations.2/ Identifying and testing new candidate genes responsible not only for typical PCD and related disorders of the axoneme, but also for so far-unexplored "syndromic forms of PCD", taking advantage of data obtained through comparative genomic approaches between different species, ciliated or not.

  Eligibility

Ages Eligible for Study:   1 Month and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients with suspected or confirmed primary ciliary dyskinesia (followed by the participating centers)

Criteria

Inclusion Criteria:

  • Patients with suspected or confirmed primary ciliary dyskinesia after ciliary investigations who accepted to participate to the genetic studies.

Exclusion Criteria:

  • Patients with exclusion of primary ciliary dyskinesia after ciliary investigations.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00783887

Contacts
Contact: Serge AMSELEM, MD, PhD +33 (0) 1 44 73 52 39 serge.amselem@trs.aphp.fr
Contact: Estelle ESCUDIER, MD +33 (0) 1 44 73 52 39 estelle.escudier@trs.aphp.fr

Locations
France
Hôpital A. Trousseau, Service de Génétique et d'Embryologie Médicales Recruiting
Paris, France, 75012
Contact: Serge AMSELEM, MD, PhD     +33 (0) 1 44 73 52 39     serge.amselem@trs.aphp.fr    
Principal Investigator: Estelle ESCUDIER, MD            
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Serge AMSELEM, MD PhD Assistance Publique - Hôpitaux de Paris
  More Information

Publications:
Bush A, Cole P, Hariri M, Mackay I, Phillips G, O'Callaghan C, Wilson R, Warner JO. Primary ciliary dyskinesia: diagnosis and standards of care. Eur Respir J. 1998 Oct;12(4):982-8. Review.
Noone PG, Leigh MW, Sannuti A, Minnix SL, Carson JL, Hazucha M, Zariwala MA, Knowles MR. Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med. 2004 Feb 15;169(4):459-67. Epub 2003 Dec 4.
Holzmann D, Ott PM, Felix H. Diagnostic approach to primary ciliary dyskinesia: a review. Eur J Pediatr. 2000 Jan-Feb;159(1-2):95-8. Review.
Afzelius BA, Gargani G, Romano C. Abnormal length of cilia as a possible cause of defective mucociliary clearance. Eur J Respir Dis. 1985 Mar;66(3):173-80.
Escudier E, Escalier D, Pinchon MC, Boucherat M, Bernaudin JF, Fleury-Feith J. Dissimilar expression of axonemal anomalies in respiratory cilia and sperm flagella in infertile men. Am Rev Respir Dis. 1990 Sep;142(3):674-9.
Verra F, Fleury-Feith J, Boucherat M, Pinchon MC, Bignon J, Escudier E. Do nasal ciliary changes reflect bronchial changes? An ultrastructural study. Am Rev Respir Dis. 1993 Apr;147(4):908-13.
Wodehouse T, Kharitonov SA, Mackay IS, Barnes PJ, Wilson R, Cole PJ. Nasal nitric oxide measurements for the screening of primary ciliary dyskinesia. Eur Respir J. 2003 Jan;21(1):43-7.
Arnal JF, Flores P, Rami J, Murris-Espin M, Bremont F, Pasto I Aguilla M, Serrano E, Didier A. Nasal nitric oxide concentration in paranasal sinus inflammatory diseases. Eur Respir J. 1999 Feb;13(2):307-12.
Karadag B, James AJ, Gültekin E, Wilson NM, Bush A. Nasal and lower airway level of nitric oxide in children with primary ciliary dyskinesia. Eur Respir J. 1999 Jun;13(6):1402-5.
Rossman CM, Lee RM, Forrest JB, Newhouse MT. Nasal cilia in normal man, primary ciliary dyskinesia and other respiratory diseases: analysis of motility and ultrastructure. Eur J Respir Dis Suppl. 1983;127:64-70.
Chilvers MA, Rutman A, O'Callaghan C. Functional analysis of cilia and ciliated epithelial ultrastructure in healthy children and young adults. Thorax. 2003 Apr;58(4):333-8.
Tamalet A, Clement A, Roudot-Thoraval F, Desmarquest P, Roger G, Boulé M, Millepied MC, Baculard TA, Escudier E. Abnormal central complex is a marker of severity in the presence of partial ciliary defect. Pediatrics. 2001 Nov;108(5):E86.
Moore A, Escudier E, Roger G, Tamalet A, Pelosse B, Marlin S, Clément A, Geremek M, Delaisi B, Bridoux AM, Coste A, Witt M, Duriez B, Amselem S. RPGR is mutated in patients with a complex X linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa. J Med Genet. 2006 Apr;43(4):326-33. Epub 2005 Jul 31.
Krawczyński MR, Witt M. PCD and RP: X-linked inheritance of both disorders? Pediatr Pulmonol. 2004 Jul;38(1):88-9.
Pennarun G, Escudier E, Chapelin C, Bridoux AM, Cacheux V, Roger G, Clément A, Goossens M, Amselem S, Duriez B. Loss-of-function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia. Am J Hum Genet. 1999 Dec;65(6):1508-19.
Porter ME. Axonemal dyneins: assembly, organization, and regulation. Curr Opin Cell Biol. 1996 Feb;8(1):10-7. Review.
Porter ME, Sale WS. The 9 + 2 axoneme anchors multiple inner arm dyneins and a network of kinases and phosphatases that control motility. J Cell Biol. 2000 Nov 27;151(5):F37-42. Review. No abstract available.
Zariwala M, Noone PG, Sannuti A, Minnix S, Zhou Z, Leigh MW, Hazucha M, Carson JL, Knowles MR. Germline mutations in an intermediate chain dynein cause primary ciliary dyskinesia. Am J Respir Cell Mol Biol. 2001 Nov;25(5):577-83.
Guichard C, Harricane MC, Lafitte JJ, Godard P, Zaegel M, Tack V, Lalau G, Bouvagnet P. Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome). Am J Hum Genet. 2001 Apr;68(4):1030-5. Epub 2001 Feb 23.
Dutcher SK. Chlamydomonas reinhardtii: biological rationale for genomics. J Eukaryot Microbiol. 2000 Jul-Aug;47(4):340-9.
Kamiya R. Functional diversity of axonemal dyneins as studied in Chlamydomonas mutants. Int Rev Cytol. 2002;219:115-55. Review.
Pennarun G, Chapelin C, Escudier E, Bridoux AM, Dastot F, Cacheux V, Goossens M, Amselem S, Duriez B. The human dynein intermediate chain 2 gene (DNAI2): cloning, mapping, expression pattern, and evaluation as a candidate for primary ciliary dyskinesia. Hum Genet. 2000 Dec;107(6):642-9.
Bartoloni L, Blouin JL, Maiti AK, Sainsbury A, Rossier C, Gehrig C, She JX, Marron MP, Lander ES, Meeks M, Chung E, Armengot M, Jorissen M, Scott HS, Delozier-Blanchet CD, Gardiner RM, Antonarakis SE. Axonemal beta heavy chain dynein DNAH9: cDNA sequence, genomic structure, and investigation of its role in primary ciliary dyskinesia. Genomics. 2001 Feb 15;72(1):21-33.
Pennarun G, Bridoux AM, Escudier E, Dastot-Le Moal F, Cacheux V, Amselem S, Duriez B. Isolation and expression of the human hPF20 gene orthologous to Chlamydomonas PF20: evaluation as a candidate for axonemal defects of respiratory cilia and sperm flagella. Am J Respir Cell Mol Biol. 2002 Mar;26(3):362-70.
Omran H, Häffner K, Völkel A, Kuehr J, Ketelsen UP, Ross UH, Konietzko N, Wienker T, Brandis M, Hildebrandt F. Homozygosity mapping of a gene locus for primary ciliary dyskinesia on chromosome 5p and identification of the heavy dynein chain DNAH5 as a candidate gene. Am J Respir Cell Mol Biol. 2000 Nov;23(5):696-702.
Olbrich H, Häffner K, Kispert A, Völkel A, Volz A, Sasmaz G, Reinhardt R, Hennig S, Lehrach H, Konietzko N, Zariwala M, Noone PG, Knowles M, Mitchison HM, Meeks M, Chung EM, Hildebrandt F, Sudbrak R, Omran H. Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. Nat Genet. 2002 Feb;30(2):143-4. Epub 2002 Jan 14.
Bartoloni L, Blouin JL, Pan Y, Gehrig C, Maiti AK, Scamuffa N, Rossier C, Jorissen M, Armengot M, Meeks M, Mitchison HM, Chung EM, Delozier-Blanchet CD, Craigen WJ, Antonarakis SE. Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia. Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10282-6. Epub 2002 Jul 25.
Volz A, Boyle JM, Cann HM, Cottingham RW, Orr HT, Ziegler A. Report of the Second International Workshop on Human Chromosome 6. Genomics. 1994 May 15;21(2):464-72. No abstract available.
Meeks M, Walne A, Spiden S, Simpson H, Mussaffi-Georgy H, Hamam HD, Fehaid EL, Cheehab M, Al-Dabbagh M, Polak-Charcon S, Blau H, O'Rawe A, Mitchison HM, Gardiner RM, Chung E. A locus for primary ciliary dyskinesia maps to chromosome 19q. J Med Genet. 2000 Apr;37(4):241-4.
Witt M, Wang Y, Wang S, Sun C, Pawlik J, Rutkiewicz E, Zebrak J, Diehl SR. Exclusion of chromosome 7 for Kartagener syndrome but suggestion of linkage in families with other forms of primary ciliary dyskinesia. Am J Hum Genet. 1999 Jan;64(1):313-8. No abstract available.
Geremek M, Zietkiewicz E, Diehl SR, Alizadeh BZ, Wijmenga C, Witt M. Linkage analysis localises a Kartagener syndrome gene to a 3.5 cM region on chromosome 15q24-25. J Med Genet. 2006 Jan;43(1):e1.
Jeganathan D, Chodhari R, Meeks M, Faeroe O, Smyth D, Nielsen K, Amirav I, Luder AS, Bisgaard H, Gardiner RM, Chung EM, Mitchison HM. Loci for primary ciliary dyskinesia map to chromosome 16p12.1-12.2 and 15q13.1-15.1 in Faroe Islands and Israeli Druze genetic isolates. J Med Genet. 2004 Mar;41(3):233-40. No abstract available.
Blouin JL, Meeks M, Radhakrishna U, Sainsbury A, Gehring C, Saïl GD, Bartoloni L, Dombi V, O'Rawe A, Walne A, Chung E, Afzelius BA, Armengot M, Jorissen M, Schidlow DV, van Maldergem L, Walt H, Gardiner RM, Probst D, Guerne PA, Delozier-Blanchet CD, Antonarakis SE. Primary ciliary dyskinesia: a genome-wide linkage analysis reveals extensive locus heterogeneity. Eur J Hum Genet. 2000 Feb;8(2):109-18.
Chilvers MA, Rutman A, O'Callaghan C. Ciliary beat pattern is associated with specific ultrastructural defects in primary ciliary dyskinesia. J Allergy Clin Immunol. 2003 Sep;112(3):518-24.
Rutland J, Cox T, Dewar A, Cole P. Screening for ciliary dyskinesia - a spectrum of defects of motility and structure. Eur J Respir Dis Suppl. 1983;127:71-7.
de Iongh RU, Rutland J. Ciliary defects in healthy subjects, bronchiectasis, and primary ciliary dyskinesia. Am J Respir Crit Care Med. 1995 May;151(5):1559-67.
Cazeneuve C, Ajrapetyan H, Papin S, Roudot-Thoraval F, Geneviève D, Mndjoyan E, Papazian M, Sarkisian A, Babloyan A, Boissier B, Duquesnoy P, Kouyoumdjian JC, Girodon-Boulandet E, Grateau G, Sarkisian T, Amselem S. Identification of MEFV-independent modifying genetic factors for familial Mediterranean fever. Am J Hum Genet. 2000 Nov;67(5):1136-43. Epub 2000 Oct 3.

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT00783887     History of Changes
Other Study ID Numbers: AOM 06053
Study First Received: October 31, 2008
Last Updated: December 26, 2011
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Cilia
Axoneme
Dynein
 Gene
Ultrastructure
Linkage analysis

Additional relevant MeSH terms:
Ciliary Motility Disorders
Kartagener Syndrome
Dyskinesias
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Bronchiectasis
Bronchial Diseases
Respiratory System Abnormalities
Dextrocardia
Heart Defects, Congenital
Cardiovascular Abnormalities
 Cardiovascular Diseases
Heart Diseases
Congenital Abnormalities
Situs Inversus
Genetic Diseases, Inborn
Movement Disorders
Central Nervous System Diseases
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms

ClinicalTrials.gov processed this record on February 09, 2012



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