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Clinical and genetic analysis of a family with Kartagener syndrome caused by novel DNAH5 mutations

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Kartagener syndrome (KS), also known as visceral inversion-nasosinusitis-bronchiectasis syndrome, or familial bronchiectasis, is an autosomal recessive inherited disease. In this study, through two cases of KS, we aimed to assess the clinical and genetic characteristics of KS caused by DNAH5 mutations.

Methods

The two cases of KS from the same family underwent extensive clinical assessments, with next-generation DNA sequencing and bioinformatics analysis to identify pathogenic genes. In addition, Sanger sequencing was used to verify the pedigrees.

Results

The present study employed a directional capture strategy for hereditary disease screening, which correctly identified the virulence sites in the pedigree, and facilitated the differential diagnosis among multiple genes. Two novel mutations were detected in DNAH5: c.7778C>T (missense mutation) and c.13729G>A (nonsense mutation). They were not found in dbSNP, 1000 Genomes, and ExAC.

Conclusions

These findings demonstrated that new DNAH5 mutations could be used for molecular diagnosis of KS, providing families with genetic counseling and prenatal diagnosis.

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References

  1. Moore A, Escudier E, Roger G, Tamalet A, Pelosse B, Marlin S, et al. RPGR is mutated in patients with a complex X linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa. J Med Genet. 2006;43(4):326–33. doi:10.1136/jmg.2005.034868.

    Article  CAS  PubMed  Google Scholar 

  2. Knowles MR, Leigh MW, Ostrowski LE, Huang L, Carson JL, Hazucha MJ, et al. Exome sequencing identifies mutations in CCDC114 as a cause of primary ciliary dyskinesia. Am J Hum Genet. 2013;92(1):99–106. doi:10.1016/j.ajhg.2012.11.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Afzelius B, Mossberg B, Bergstrom S. Immotile-cilia syndrome (primary ciliary dyskinesia), including Kartagener syndrome. Metabol Molecul Base Inherit Dis. 1995;3:3943–54.

    Google Scholar 

  4. Kennedy MP, Omran H, Leigh MW, Dell S, Morgan L, Molina PL, et al. Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation. 2007;115(22):2814–21. doi:10.1161/CIRCULATIONAHA.106.649038.

    Article  PubMed  Google Scholar 

  5. Hogg C, Bush A. Genotyping in primary ciliary dyskinesia: ready for prime time, or a fringe benefit? Thorax. 2012;67(5):377–8. doi:10.1136/thoraxjnl-2011-201320.

    Article  PubMed  Google Scholar 

  6. O’Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S, et al. Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat Genet. 2011;43(6):585–9. doi:10.1038/ng.835.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Geremek M, Schoenmaker F, Zietkiewicz E, Pogorzelski A, Diehl S, Wijmenga C, et al. Sequence analysis of 21 genes located in the Kartagener syndrome linkage region on chromosome 15q. Euro J Hum Genet: EJHG. 2008;16(6):688–95. doi:10.1038/ejhg.2008.5.

    Article  CAS  Google Scholar 

  8. Djakow J, Svobodova T, Hrach K, Uhlik J, Cinek O, Pohunek P. Effectiveness of sequencing selected exons of DNAH5 and DNAI1 in diagnosis of primary ciliary dyskinesia. Pediatr Pulmonol. 2012;47(9):864–75. doi:10.1002/ppul.22520.

    Article  PubMed  Google Scholar 

  9. Failly M, Bartoloni L, Letourneau A, Munoz A, Falconnet E, Rossier C, et al. Mutations in DNAH5 account for only 15% of a non-preselected cohort of patients with primary ciliary dyskinesia. J Med Genet. 2009;46(4):281–6. doi:10.1136/jmg.2008.061176.

    Article  CAS  PubMed  Google Scholar 

  10. Fliegauf M, Olbrich H, Horvath J, Wildhaber JH, Zariwala MA, Kennedy M, et al. Mislocalization of DNAH5 and DNAH9 in respiratory cells from patients with primary ciliary dyskinesia. Am J Respir Crit Care Med. 2005;171(12):1343–9. doi:10.1164/rccm.200411-1583OC.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Jorissen M, Willems T, Van der Schueren B, Verbeken E, De Boeck K. Ultrastructural expression of primary ciliary dyskinesia after ciliogenesis in culture. Acta Otorhinolaryngol Belg. 2000;54(3):343–56.

    CAS  PubMed  Google Scholar 

  12. Afzelius BA. A human syndrome caused by immotile cilia. Science. 1976;193(4250):317–9.

    Article  CAS  PubMed  Google Scholar 

  13. Geremek M, Witt M. Primary ciliary dyskinesia: genes, candidate genes and chromosomal regions. J Appl Genet. 2004;45(3):347–61.

    PubMed  Google Scholar 

  14. Noone PG, Leigh MW, Sannuti A, Minnix SL, Carson JL, Hazucha M, et al. Primary ciliary dyskinesia: diagnostic and phenotypic features. Am J Respir Crit Care Med. 2004;169(4):459–67. doi:10.1164/rccm.200303-365OC.

    Article  PubMed  Google Scholar 

  15. Halbert SA, Patton DL, Zarutskie PW, Soules MR. Function and structure of cilia in the fallopian tube of an infertile woman with Kartagener’s syndrome. Hum Reprod. 1997;12(1):55–8.

    Article  CAS  PubMed  Google Scholar 

  16. Fischer TJ, McAdams JA, Entis GN, Cotton R, Ghory JE, Ausdenmoore RW. Middle ear ciliary defect in Kartagener’s syndrome. Pediatrics. 1978;62(4):443–5.

    CAS  PubMed  Google Scholar 

  17. Guichard C, Harricane MC, Lafitte JJ, Godard P, Zaegel M, Tack V, et al. Axonemal dynein intermediate-chain gene (DNAI1) mutations result in situs inversus and primary ciliary dyskinesia (Kartagener syndrome). Am J Hum Genet. 2001;68(4):1030–5. doi:10.1086/319511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Eliasson R, Mossberg B, Camner P, Afzelius BA. The immotile-cilia syndrome. A congenital ciliary abnormality as an etiologic factor in chronic airway infections and male sterility. N Engl J Med. 1977;297(1):1–6. doi:10.1056/NEJM197707072970101.

    Article  CAS  PubMed  Google Scholar 

  19. Hornef N, Olbrich H, Horvath J, Zariwala MA, Fliegauf M, Loges NT, et al. DNAH5 mutations are a common cause of primary ciliary dyskinesia with outer dynein arm defects. Am J Respir Crit Care Med. 2006;174(2):120–6. doi:10.1164/rccm.200601-084OC.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Afzelius BA, Eliasson R. Male and female infertility problems in the immotile-cilia syndrome. Eur J Respir Dis Suppl. 1983;127:144–7.

    CAS  PubMed  Google Scholar 

  21. Munro NC, Currie DC, Lindsay KS, Ryder TA, Rutman A, Dewar A, et al. Fertility in men with primary ciliary dyskinesia presenting with respiratory infection. Thorax. 1994;49(7):684–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Author information

Authors and Affiliations

  1. Children’s Medical Center, People’s Hospital, Changsha, Hunan Province, China, 410005

    Xuan Xu & Ping Gong

  2. Pediatric orthopedics, People’s Hospital, Changsha, Hunan Province, China, 410005

    Jie Wen

Authors
  1. Xuan Xu
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  2. Ping Gong
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  3. Jie Wen
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Corresponding author

Correspondence to Ping Gong.

Ethics declarations

Research involving human participants

The present study was approved by the Ethics Committee of People’s Hospital. All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Capsule These findings demonstrated that new DNAH5 mutations could be used for molecular diagnosis of KS, providing families with genetic counseling and prenatal diagnosis.

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Xu, X., Gong, P. & Wen, J. Clinical and genetic analysis of a family with Kartagener syndrome caused by novel DNAH5 mutations. J Assist Reprod Genet 34, 275–281 (2017). https://doi.org/10.1007/s10815-016-0849-3

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  • DOI: https://doi.org/10.1007/s10815-016-0849-3

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