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

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Title: Unexpected genetic heterogeneity for primary ciliary dyskinesia in the Irish Traveller population
Authors: Casey, Jillian
McGettigan, Paul A.
Healy, Fiona
Reynolds, Alison
Kennedy, Breandán
Ennis, Sean
Slattery, Dubhfeasa
Lynch, Sally
Hogg, Claire
Permanent link: http://hdl.handle.net/10197/5688
Date: May-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.
Type of material: Journal Article
Publisher: Nature Publishing Group
Keywords: Primary ciliary dyskinesiaIrish TravellerRSPH4ACCNODYX1C1Genetic heterogeneity
DOI: 10.1038/ejhg.2014.79
Language: en
Status of Item: Peer reviewed
Appears in Collections:Biomolecular and Biomedical Science Research Collection

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