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A Large Intragenic Deletion in the ACADM Gene Can Cause MCAD Deficiency but is not Detected on Routine Sequencing

  • Claire Searle
  • Brage Storstein Andresen
  • Ed Wraith
  • Jamie Higgs
  • Deborah Gray
  • Alison Mills
  • K. Elizabeth Allen
  • Emma Hobson
Case Report
Part of the JIMD Reports book series (JIMD, volume 11)

Abstract

We report of a family who has three members affected by medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, one of whom sadly died in the neonatal period prior to diagnosis. Routine sequencing, available on a service basis in the UK, identified only a heterozygous mutation in ACADM gene (c.985A>G, p.Lys329Glu) in this family. Linkage analysis suggested a possible intragenic deletion which was confirmed by the use of array-based comparative genomic hybridization (aCGH). This second mutation was a large intragenic deletion encompassing at least exons 1–6 of the ACADM gene. Now that this deletion has been identified, several family members have come forward for carrier testing which was not possible previously. Larger deletions (20bp or more) have only previously been reported twice, but these may be a more frequent cause of MCAD deficiency than hitherto believed, due to fact that these are not anticipated and, therefore, the routine diagnostic techniques used will not identify them. This finding represents a useful learning point in the management of families with MCAD deficiency, and highlights that we should be routinely looking for larger deletions, when only one of the mutations can be identified on standard sequencing.

Abbreviations

MCAD

Medium Chain Acyl-CoA Dehydrogenase

MLPA

Multiplex Ligation-dependent Probe Amplification

Notes

Acknowledgements

We would like to thank the family involved in this article.

References

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Claire Searle
    • 1
  • Brage Storstein Andresen
    • 2
  • Ed Wraith
    • 3
  • Jamie Higgs
    • 4
  • Deborah Gray
    • 5
  • Alison Mills
    • 5
  • K. Elizabeth Allen
    • 6
  • Emma Hobson
    • 1
  1. 1.Yorkshire Regional Genetic ServiceChapel Allerton HospitalLeedsUK
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Southern DenmarkOdenseDenmark
  3. 3.Royal Manchester Children’s HospitalManchesterUK
  4. 4.GeneDxGaithersburgUSA
  5. 5.Cytogenetics, Ashley WingSt. James’s University HospitalLeedsUK
  6. 6.Sheffield Diagnostic Genetics ServiceSheffield Children’s NHS Foundation TrustSheffieldUK

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