Unexpected Genetic Heterogeneity
Although it is generally considered that genetic disorders in the Irish Traveller population are caused by common autosomal recessive mutations, recent studies have revealed an unexpected genetic heterogeneity in certain conditions.
In a study published recently in the European Journal of Human Genetics, researchers at the UCD Academic Centre on Rare Diseases examined five children from three unrelated Irish Traveller families presenting with primary ciliary dyskinesia (PCD).
Expecting all three PCD families to share the same recessive mutation, exome sequencing showed that in fact there was no pathogenic homozygous mutation common to all families studied. This heterogeneity was confirmed by histology which showed that each family has a different type of ciliary defect.
Independent homozygosity mapping and exome sequencing of each family identified a novel genetic duplication in affected siblings from one family, three novel candidate genes implicated in the second family and in the third family, a deletion in different gene previously associated with PCD.
These results are the first reports of a disorder in the relatively small Irish Traveller population to be caused by more than a single disease gene. The identification of at least three different PCD genes in this study highlight that one cannot always assume genetic heterogeneity even in small consanguineous populations.
This work led by Dr Jillian Casey and Dr Sally Ann Lynch from the Genetics Dept at St Children’s University Hospital (Temple St), the National Children’s Research Centre (Our Lady’s Children’s Hospital, Crumlin) and the UCD Academic Centre for Rare Diseases.
Unexpected genetic heterogeneity for primary ciliary dyskinesia in the Irish Traveller population European Journal of Human Genetics
Advance online publication 14 May 2014; doi: 10.1038/ejhg.2014.791National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland2Genetics Department, Temple Street Children’s University Hospital, Dublin 1, Ireland3Academic Centre on Rare Diseases, School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin 4, Ireland4UCD School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Dublin 4, Ireland5Respiratory Department, Temple Street Children’s University Hospital, Dublin 1, Ireland6Paediatric Respiratory Department, Royal Brompton Hospital, London, UK7Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland8National Centre for Medical Genetics, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland9School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin 4, Ireland