Emma J Ashton

Publications (3)12.88 Total impact

• Article: Marked hemiatrophy in carriers of Duchenne muscular dystrophy.

  Sanjeev Rajakulendran, Thierry Kuntzer, Murielle Dunand, Shu C Yau, Emma J Ashton, Helen Storey, Joanna McCauley, Stephen Abbs, Francine Thonney, France Leturcq, Johannes A Lobrinus, Tarek Yousry, Simon Farmer, Janice L Holton, Michael G Hanna
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  ABSTRACT: To describe the clinical and molecular genetic findings in 2 carriers of Duchenne muscular dystrophy (DMD) who exhibited marked hemiatrophy. Duchenne muscular dystrophy is an X-linked disorder in which affected male patients harbor mutations in the dystrophin gene. Female patients with heterozygous mutations may be manifesting carriers. Case study. Neurology clinic. Two manifesting carriers of DMD. Clinical and radiologic examinations along with histologic and molecular investigations. Both patients had marked right-sided hemiatrophy on examination with radiologic evidence of muscle atrophy and fatty replacement on the affected side. In each case, histologic analysis revealed a reduction in dystrophin staining on the right side. Genetic analysis of the dystrophin gene revealed a tandem exonic duplication in patient 1 and a multiexonic deletion in patient 2 with no further point mutations identified on the other chromosome. Marked hemiatrophy can occur in DMD manifesting carriers. This is likely to result from a combination of skewed X-inactivation and somatic mosaicism.
  Archives of neurology 04/2010; 67(4):497-500. · 6.31 Impact Factor
• Article: Simultaneous mutation scanning for gross deletions, duplications and point mutations in the DMD gene.

  Emma J Ashton, Shu C Yau, Zandra C Deans, Stephen J Abbs
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  ABSTRACT: We have developed a technique to screen for gross deletions/duplications and point mutations using one streamlined approach. Fluorescent multiplex quantitative PCR is used to determine the copy number of each exon, followed by conformation sensitive capillary electrophoresis (CSCE) of the same PCR products on a multi-capillary genetic analyser. We have developed this technique to screen all 79 exons of one of the largest human genes currently known (dystrophin) using 12 multiplex PCR assays. A blind trial of 50 male and 50 female samples, in which 84 mutations had previously been found and characterized by other techniques, showed 100% sensitivity and specificity. We then applied this method to screen over 100 patient samples previously screened for deletions and duplications of 28 exons from the two hotspot regions. Our data show that combining a full deletion/duplication screen with CSCE will detect a mutation in 98% of Duchenne muscular dystrophy patients and 93% of Becker muscular dystrophy patients where the clinical diagnosis is certain. This technique is applicable to any gene and is particularly suited to mutation screening of large genes, decreasing the time taken for a complete gene screen for nearly all mutation types.
  European Journal of HumanGenetics 02/2008; 16(1):53-61. · 4.40 Impact Factor
• Source

  Available from: ngrl.co.uk

  Article: Simultaneous MLPA-based multiplex point mutation and deletion analysis of the dystrophin gene.

  David J Bunyan, Alison C Skinner, Emma J Ashton, Julie Sillibourne, Tom Brown, Amanda L Collins, Nicholas C P Cross, John F Harvey, David O Robinson
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  ABSTRACT: The Multiplex Ligation-dependent Probe Amplification assay (MLPA) is the method of choice for the initial mutation screen in the analysis of a large number of genes where partial or total gene deletion is part of the mutation spectrum. Although MLPA dosage probes are usually designed to bind to normal DNA sequence to identify dosage imbalance, point mutation-specific MLPA probes can also be made. Using the dystrophin gene as a model, we have designed two MLPA probe multiplexes that are specific to a number of commonly listed point mutations in the Leiden dystrophin point mutation database (http://www.dmd.nl). The point mutation probes are designed to work simultaneously with two widely used dystrophin MLPA multiplexes, allowing both full dosage analysis and partial point mutation analysis in a single test. This approach may be adapted for other syndromes with well defined common point mutations or polymorphisms.
  Molecular Biotechnology 03/2007; 35(2):135-40. · 2.17 Impact Factor