May 2014

Unexpected Genetic Heterogeneity

Tue, 20 May 14 09:00

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.

Reference:

Unexpected genetic heterogeneity for primary ciliary dyskinesia in the Irish Traveller population European Journal of Human Genetics 

Jillian P Casey1,2,3, Paul A McGettigan3,4, Fiona Healy5, Claire Hogg6, Alison Reynolds7, Breandan N Kennedy3,7, Sean Ennis3,8, Dubhfeasa Slattery5,9and Sally A Lynch2,3,8

Advance online publication 14 May 2014; doi: 10.1038/ejhg.2014.79

1National Children’s Research Centre, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland
2Genetics Department, Temple Street Children’s University Hospital, Dublin 1, Ireland
3Academic Centre on Rare Diseases, School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin 4, Ireland
4UCD School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Dublin 4, Ireland
5Respiratory Department, Temple Street Children’s University Hospital, Dublin 1, Ireland
6Paediatric Respiratory Department, Royal Brompton Hospital, London, UK
7Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland
8National Centre for Medical Genetics, Our Lady’s Children’s Hospital, Crumlin, Dublin 12, Ireland
9School of Medicine and Medical Sciences, University College Dublin, Belfield, Dublin 4, Ireland