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Detection of a dna methylation signature for the intellectual developmental disorder, x-linked, syndromic, armfield type
International Journal of Molecular Sciences
  • Sadegheh Haghshenas, Western University
  • Michael A. Levy, London Health Sciences Centre
  • Jennifer Kerkhof, London Health Sciences Centre
  • Erfan Aref-Eshghi, The Children's Hospital of Philadelphia
  • Haley McConkey, London Health Sciences Centre
  • Tugce Balci, Western University
  • Victoria Mok Siu, London Health Sciences Centre
  • Cindy D. Skinner, Greenwood Genetics Center
  • Roger E. Stevenson, Greenwood Genetics Center
  • Bekim Sadikovic, Western University
  • Charles Schwartz, Greenwood Genetics Center
Document Type
Article
Publication Date
2-1-2021
URL with Digital Object Identifier
10.3390/ijms22031111
Abstract

A growing number of genetic neurodevelopmental disorders are known to be associated with unique genomic DNA methylation patterns, called episignatures, which are detectable in peripheral blood. The intellectual developmental disorder, X-linked, syndromic, Armfield type (MRXSA) is caused by missense variants in FAM50A. Functional studies revealed the pathogenesis to be a spliceosomopathy that is characterized by atypical mRNA processing during development. In this study, we assessed the peripheral blood specimens in a cohort of individuals with MRXSA and detected a unique and highly specific DNA methylation episignature associated with this disorder. We used this episignature to construct a support vector machine model capable of sensitive and specific identification of individuals with pathogenic variants in FAM50A. This study contributes to the expanding number of genetic neurodevelopmental disorders with defined DNA methylation episignatures, provides an additional understanding of the associated molecular mechanisms, and further enhances our ability to diagnose patients with rare disorders.

Citation Information
Sadegheh Haghshenas, Michael A. Levy, Jennifer Kerkhof, Erfan Aref-Eshghi, et al.. "Detection of a dna methylation signature for the intellectual developmental disorder, x-linked, syndromic, armfield type" International Journal of Molecular Sciences Vol. 22 Iss. 3 (2021) p. 1 - 13
Available at: http://works.bepress.com/bekim-sadikovic/13/