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  5. Unexpected genetic heterogeneity for primary ciliary dyskinesia in the Irish Traveller population
 
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Unexpected genetic heterogeneity for primary ciliary dyskinesia in the Irish Traveller population

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Author(s)
Casey, Jillian 
McGettigan, Paul A. 
Healy, Fiona 
Reynolds, Alison 
Kennedy, Breandán 
Ennis, Sean 
Slattery, Dubhfeasa 
Lynch, Sally 
Hogg, Claire 
Uri
http://hdl.handle.net/10197/5688
Date Issued
May 2014
Date Available
04T13:55:28Z July 2014
Abstract
We present a study of five children from three unrelated Irish Traveller families presenting with primary ciliary dyskinesia (PCD). As previously characterized disorders in the Irish Traveller population are caused by common homozygous mutations, we hypothesised that all three PCD families shared the same recessive mutation. However, exome sequencing showed that there was no pathogenic homozygous mutation common to all families. This finding was supported by histology, which showed that each family has a different type of ciliary defect; transposition defect (family A), nude epithelium (family B) and absence of inner and outer dynein arms (family C). Therefore, each family was analysed independently using homozygosity mapping and exome sequencing. The affected siblings in family A share a novel 1 bp duplication in RSPH4A (NM_001161664.1:c.166dup; p.Arg56Profs*11), a radial-spoke head protein involved in ciliary movement. In family B, we identified three candidate genes (CCNO, KCNN3 and CDKN1C), with a 5-bp duplication in CCNO (NM_021147.3:c.258_262dup; p.Gln88Argfs*8) being the most likely cause of ciliary aplasia. This is the first study to implicate CCNO, a DNA repair gene reported to be involved in multiciliogenesis, in PCD. In family C, we identified a ~3.5-kb deletion in DYX1C1, a neuronal migration gene previously associated with PCD. This is the first report of a disorder in the relatively small Irish Traveller population to be caused by >1 disease gene. Our study identified at least three different PCD genes in the Irish Traveller population, highlighting that one cannot always assume genetic homogeneity, even in small consanguineous populations.
Other Sponsorship
Children's Fund for Health
The Fundraising Office for Temple Street Children's Hospital
Medical Research Charities Group Grant, National Children's Research Centre
Health Research Board
Type of Material
Journal Article
Publisher
Nature Publishing Group
Journal
European Journal of Human Genetics
Issue
May 14th 2014
Keywords
  • Primary ciliary dyski...

  • Irish Traveller

  • RSPH4A

  • CCNO

  • DYX1C1

  • Genetic heterogeneity...

DOI
10.1038/ejhg.2014.79
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
https://creativecommons.org/licenses/by-nc-nd/3.0/ie/
Owning collection
Biomolecular and Biomedical Science Research Collection
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Mar 29, 2023
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