Diagnosis of Primary Ciliary Dyskinesia

NCT00783887 | Completed

• 1 other identifier: AOM 06053
• Study Type: observational
• Target: 125
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Primary Ciliary Dyskinesia; Kartagener Syndrome

Keywords

Cilia; Axoneme; Dynein; Gene; Ultrastructure; Linkage analysis

Outcome Measures

Primary Outcomes (1)

• After DNA extraction,standard procedures for the identification of human gene mutations will be used for each gene tested in the study

  At the inclusion visit

Secondary Outcomes (1)

• Complementary ciliary investigations in patients with suspected primary ciliary dyskinesia.

  At the inclusion visit

Study Arms (1)

1

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

Other: Blood sample

Interventions

Blood sample OTHER

Blood sample of 5 ml

1

Eligibility Criteria

• Age: 1 Month+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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

You may qualify if:

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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital A. Trousseau, Service de Génétique et d'Embryologie Médicales

Paris, 75012, France

Location

Related Publications (37)

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• Tamalet A, Clement A, Roudot-Thoraval F, Desmarquest P, Roger G, Boule 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. doi: 10.1542/peds.108.5.e86.

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• Moore A, Escudier E, Roger G, Tamalet A, Pelosse B, Marlin S, Clement 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. doi: 10.1136/jmg.2005.034868. Epub 2005 Jul 31.

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• Krawczynski MR, Witt M. PCD and RP: X-linked inheritance of both disorders? Pediatr Pulmonol. 2004 Jul;38(1):88-9. doi: 10.1002/ppul.30001.

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• Pennarun G, Escudier E, Chapelin C, Bridoux AM, Cacheux V, Roger G, Clement 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. doi: 10.1086/302683.

  PMID: 10577904 BACKGROUND

• Porter ME. Axonemal dyneins: assembly, organization, and regulation. Curr Opin Cell Biol. 1996 Feb;8(1):10-7. doi: 10.1016/s0955-0674(96)80042-1.

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• 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. doi: 10.1083/jcb.151.5.f37. No abstract available.

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• 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. doi: 10.1165/ajrcmb.25.5.4619.

  PMID: 11713099 BACKGROUND

• 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. doi: 10.1086/319511. Epub 2001 Feb 23.

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• Dutcher SK. Chlamydomonas reinhardtii: biological rationale for genomics. J Eukaryot Microbiol. 2000 Jul-Aug;47(4):340-9. doi: 10.1111/j.1550-7408.2000.tb00059.x.

  PMID: 11140447 BACKGROUND

• Kamiya R. Functional diversity of axonemal dyneins as studied in Chlamydomonas mutants. Int Rev Cytol. 2002;219:115-55. doi: 10.1016/s0074-7696(02)19012-7.

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• 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. doi: 10.1007/s004390000427.

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• 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. doi: 10.1006/geno.2000.6462.

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• 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. doi: 10.1165/ajrcmb.26.3.4738.

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• Omran H, Haffner K, Volkel 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. doi: 10.1165/ajrcmb.23.5.4257.

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• Olbrich H, Haffner K, Kispert A, Volkel 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. doi: 10.1038/ng817. Epub 2002 Jan 14.

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• 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. doi: 10.1073/pnas.152337699. Epub 2002 Jul 25.

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• Witt M, Wang Yf, Wang S, Sun Ce, 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. doi: 10.1086/302203. No abstract available.

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• 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. doi: 10.1136/jmg.2005.031526.

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• 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. doi: 10.1136/jmg.2003.014084. No abstract available.

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• 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. doi: 10.1016/s0091-6749(03)01799-8.

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• Cazeneuve C, Ajrapetyan H, Papin S, Roudot-Thoraval F, Genevieve 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. doi: 10.1016/S0002-9297(07)62944-9. Epub 2000 Oct 3.

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Biospecimen

Retention: SAMPLES WITH DNA

DNA, Serum, White blood cells

MeSH Terms

Conditions

Ciliary Motility Disorders; Kartagener Syndrome

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Bronchiectasis; Bronchial Diseases; Respiratory System Abnormalities; Dextrocardia; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Situs Inversus

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Serge AMSELEM, MD PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2008
• First Posted: November 3, 2008
• Study Start: January 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 7, 2013

Record last verified: 2013-08

Locations

FR (1)