Journal article
Challenges of diagnostic exome sequencing in an inbred founder population
DN Azmanov, T Chamova, R Tankard, V Gelev, M Bynevelt, L Florez, D Tzoneva, D Zlatareva, V Guergueltcheva, M Bahlo, I Tournev, L Kalaydjieva
Molecular Genetics and Genomic Medicine | WILEY | Published : 2013
DOI: 10.1002/mgg3.7
Open access
Abstract
Exome sequencing was used as a diagnostic tool in a Roma/Gypsy family with three subjects (one deceased) affected by lissencephaly with cerebellar hypoplasia (LCH), a clinically and genetically heterogeneous diagnostic category. Data analysis identified high levels of unreported inbreeding, with multiple rare/novel “deleterious” variants occurring in the homozygous state in the affected individuals. Step-wise filtering was facilitated by the inclusion of parental samples in the analysis and the availability of ethnically matched control exome data. We identified a novel mutation, p.Asp487Tyr, in the VLDLR gene involved in the Reelin developmental pathway and associated with a rare form of LC..
View full abstractGrants
Awarded by NHMRC Training Fellowship
Awarded by Australian Research Council Future Fellowship
Awarded by NHMRC Program
Funding Acknowledgements
We are grateful to the affected family and control individuals participating in this study. D. N. A. is supported by NHMRC Training Fellowship 634551. The study of D. N. A., L. F., and L. K. is supported by Medical and Health Research Infrastructure Fund, Western Australia and by the Western Australian Institute for Medical Research. M. B. is supported by Australian Research Council Future Fellowship FT100100764 and NHMRC Program Grant 490037. The study of M. B. and R. T. is supported by Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC Independent Research Institute Infrastructure Support Scheme.