期刊论文详细信息
BMC Medical Genetics
A case report of primary ciliary dyskinesia, laterality defects and developmental delay caused by the co-existence of a single gene and chromosome disorder
Sally Ann Lynch1  Basil Elnazir5  Jane S. Lucas2  David R. Betts1  Sean Ennis4  Martin White4  Jennifer McDaid1  Patricia Goggin2  Jillian P. Casey3 
[1]National Centre for Medical Genetics, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland
[2]Primary Ciliary Dyskinesia Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, UK
[3]UCD Academic Centre on Rare Diseases, School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin 4, Ireland
[4]Neonatology, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland
[5]Pediatric Respiratory Medicine, The Adelaide and Meath Hospital, Tallaght, Dublin 24, Ireland
关键词: Microduplication syndrome;    Chromosome disorder;    Single gene disorder;    Developmental delay;    Laterality defects;    Primary ciliary dyskinesia;   
Others  :  1220335
DOI  :  10.1186/s12881-015-0192-z
 received in 2014-12-11, accepted in 2015-06-22, published in 16
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【 摘 要 】

Background

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.

【 授权许可】

   
2015 Casey et al.

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