Journal article
Delayed diagnosis of congenital myasthenia due to associated mitochondrial enzyme defect
Y Guo, MJ Menezes, MP Menezes, J Liang, D Li, LG Riley, NF Clarke, PI Andrews, L Tian, R Webster, F Wang, X Liu, Y Shen, DR Thorburn, BJ Keating, A Engel, H Hakonarson, J Christodoulou, X Xu
Neuromuscular Disorders | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2015
Abstract
Clinical phenotypes of congenital myasthenic syndromes and primary mitochondrial disorders share significant overlap in their clinical presentations, leading to challenges in making the correct diagnosis. Next generation sequencing is transforming molecular diagnosis of inherited neuromuscular disorders by identifying novel disease genes and by identifying previously known genes in undiagnosed patients. This is evident in two patients who were initially suspected to have a mitochondrial myopathy, but in whom a clear diagnosis of congenital myasthenic syndromes was made through whole exome sequencing. In patient 1, whole exome sequencing revealed compound heterozygous mutations c.1228C > T (p..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank Simone Tregoning and Wendy Salter, Murdoch Childrens Research Institute, Melbourne, for enzyme assays and Rachael Duff from the West Australian Institute for Medical Research, Perth, for undertaking the mtDNA sequencing in patient 1.This research was supported by Australian NHMRC grant 1026891 to J.C., an NHMRC Principal Research Fellowship (number 1022896) to D.R.T and an Australian Mitochondrial Disease Foundation (AMDF) PhD Scholarship to M.J.M, an NIH Research Grant NS6277 to A.G.E, and a Research Grant from the Shenzhen Municipal Government of China (NO.CXZZ20130517144604091) to X.X. We would also like to acknowledge the Institutional Development Funds to Dr. Hakon Hakonarson in the Center for Applied Genomics (CAG) at the Children's Hospital of Philadelphia (CHOP). We also gratefully acknowledge donations to J.C. by the Crane and Perkins families