Type

Journal Article

Authors

Claire Hogg
Sally Lynch
Dubhfeasa Slattery
Sean Ennis
Breandán Kennedy
Alison Reynolds
Fiona Healy
Paul A. McGettigan
Jillian Casey

Subjects

Biology

Topics
irish population irish traveller dyx1c1 genetic heterogeneity ccno rsph4a primary ciliary dyskinesia dna repair

Unexpected genetic heterogeneity for primary ciliary dyskinesia in the Irish Traveller population (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.
Collections Ireland -> University College Dublin -> Biomolecular and Biomedical Science Research Collection
Ireland -> University College Dublin -> College of Science
Ireland -> University College Dublin -> School of Biomolecular & Biomedical Science

Full list of authors on original publication

Claire Hogg, Sally Lynch, Dubhfeasa Slattery, Sean Ennis, Breandán Kennedy, Alison Reynolds, Fiona Healy, Paul A. McGettigan, Jillian Casey

Experts in our system

1
Sally Ann Lynch
University College Dublin
Total Publications: 32
 
2
Sean Ennis
University College Dublin
Total Publications: 52
 
3
Breandán N Kennedy
University College Dublin
Total Publications: 55
 
4
Alison Reynolds
University College Dublin
Total Publications: 20
 
5
Paul A. McGettigan
University College Dublin
Total Publications: 46
 
6
Jillian Casey
University College Dublin
Total Publications: 24