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

BMC Medical Genetics

Case Report

Jillian P. Casey¹  Sally Ann Lynch²  Jennifer McDaid³  David R. Betts³  Martin White⁴  Basil Elnazir⁵  Jane S. Lucas⁶  Patricia Goggin⁶  Sean Ennis⁷ 

[1]Genetics Department, Temple Street Children’s University Hospital, Dublin 1, Ireland

[2]UCD Academic Centre on Rare Diseases, School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin 4, Ireland

[3]Genetics Department, Temple Street Children’s University Hospital, Dublin 1, Ireland

[4]UCD Academic Centre on Rare Diseases, School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin 4, Ireland

[5]National Centre for Medical Genetics, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland

[6]National Centre for Medical Genetics, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland

[7]Neonatology, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland

[8]Pediatric Respiratory Medicine, The Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland

[9]Primary Ciliary Dyskinesia Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK

[10]UCD Academic Centre on Rare Diseases, School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin 4, Ireland

[11]Neonatology, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland

关键词: Primary ciliary dyskinesia;    Laterality defects;    Developmental delay;    Single gene disorder;    Chromosome disorder;    Microduplication syndrome;   

DOI  :  10.1186/s12881-015-0192-z

 received in 2014-12-11, accepted in 2015-06-22,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundPrimary 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 presentationIn 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.ConclusionWe 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.

【 授权许可】

CC BY   
© Casey et al. 2015