A case report of primary ciliary dyskinesia, laterality defects and developmental delay caused by the co-existence of a single gene and chromosome disorder

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dc.contributor.authorCasey, Jillian-
dc.contributor.authorGoggin, Patricia-
dc.contributor.authorMcDaid, Jennifer-
dc.contributor.authorEnnis, Sean-
dc.contributor.authorLynch, Sally-
dc.contributor.authoret al.-
dc.date.copyright2015 the Authorsen
dc.identifier.citationBMC Medical Geneticsen
dc.description.abstractBackground: Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder characterised by abnormal ciliary motion and impaired mucociliary clearance, leading to recurrent respiratory infections, sinusitis, otitis media and male infertility. Some patients also have laterality defects. We recently reported the identification of three disease-causing PCD genes in the Irish Traveller population; RSPH4A, DYX1C1 and CCNO. We have since assessed an additional Irish Traveller family with a complex phenotype involving PCD who did not have any of the previously identified PCD mutations. Case presentation: In this study we report on a family with three children with PCD and various laterality defects. In addition, one child (V:1) has mild-to-moderate developmental delay and one child has speech delay (V:2). Developmental delay is not usually associated with PCD and is likely to be caused by an additional genetic abnormality. Transmission electron microscopy showed variable inner and outer dynein arm defects. Exome sequencing identified a homozygous missense variant in CCDC103 (c.461A > C; p.His154Pro) as the most likely cause of the PCD and laterality defects in this family. However, as mutation in CCDC103 would not account for the developmental delay, array comparative genomic hybridisation was undertaken and identified a maternally inherited gain of ~1.6 Mb (chr17:34,611,352-36,248,918). Gains at this locus are associated with 17q12 duplication syndrome which includes speech and language delay. Conclusion: We report on a variable and complex phenotype caused by the co-inheritance of a single gene mutation in CCDC103 and a microduplication at 17q12, both on chromosome 17. The co-existence of a single gene and chromosome disorder is unusual but accounts for the spectrum of clinical features in this family. In addition, our study brings the total number of PCD genes in the Irish Traveller population to four and we suspect additional PCD genes are yet to be identified. Although, on a global scale, PCD is associated with extensive genetic heterogeneity, finding such a high number of causative PCD genes within the relatively small Irish Traveller population was unexpected.en
dc.description.sponsorshipHealth Research Boarden
dc.publisherBioMed Centralen
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stateden
dc.subjectPrimary ciliary dyskinesiaen
dc.subjectLaterality defectsen
dc.subjectDevelopmental delayen
dc.subjectSingle gene disorderen
dc.subjectChromosome disorderen
dc.subjectMicroduplication syndromeen
dc.titleA case report of primary ciliary dyskinesia, laterality defects and developmental delay caused by the co-existence of a single gene and chromosome disorderen
dc.typeJournal Articleen
dc.statusPeer revieweden
dc.neeo.contributoret al.||aut|-
dc.description.othersponsorshipChildren's Fund for Health Temple Streeten
dc.description.othersponsorshipMedical Research Charities Groupen
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