Journal article

Challenges of diagnostic exome sequencing in an inbred founder population.

Dimitar N Azmanov, Teodora Chamova, Rick Tankard, Vladimir Gelev, Michael Bynevelt, Laura Florez, Dochka Tzoneva, Dora Zlatareva, Velina Guergueltcheva, Melanie Bahlo, Ivailo Tournev, Luba Kalaydjieva

Molecular Genetics and Genomic Medicine | Published : 2013


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..

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University of Melbourne Researchers