Whole exome sequencing in foetal akinesia expands the genotype-phenotype spectrum of GBE1 glycogen storage disease mutations.

Western Australian Institute for Medical Research and the Centre for Medical Research, University of Western Australia, Nedlands, Western Australia, Australia. gina.ravenscroft@uwa.edu.au

Neuromuscular disorders : NMD 2013 Feb

filter terms:

The clinically and genetically heterogenous foetal akinesias have low rates of genetic diagnosis. Exome sequencing of two siblings with phenotypic lethal multiple pterygium syndrome identified compound heterozygozity for a known splice site mutation (c.691+2T>C) and a novel missense mutation (c.956A>G; p.His319Arg) in glycogen branching enzyme 1 (GBE1). GBE1 mutations cause glycogen storage disease IV (GSD IV), including a severe foetal akinesia sub-phenotype. Re-investigating the muscle pathology identified storage material, consistent with GSD IV, which was confirmed biochemically. This study highlights the power of exome sequencing in genetically heterogeneous diseases and adds multiple pterygium syndrome to the phenotypic spectrum of GBE1 mutation. Copyright © 2012 Elsevier B.V. All rights reserved.

Citation

Gianina Ravenscroft, Elizabeth M Thompson, Emily J Todd, Kyle S Yau, Nina Kresoje, Padma Sivadorai, Kathryn Friend, Kate Riley, Nicholas D Manton, Peter Blumbergs, Michael Fietz, Rachael M Duff, Mark R Davis, Richard J Allcock, Nigel G Laing. Whole exome sequencing in foetal akinesia expands the genotype-phenotype spectrum of GBE1 glycogen storage disease mutations. Neuromuscular disorders : NMD. 2013 Feb;23(2):165-9