Human Genetics

, Volume 133, Issue 11, pp 1359–1367 | Cite as

De novo MECP2 duplications in two females with intellectual disability and unfavorable complete skewed X-inactivation

  • Nathalie Fieremans
  • Marijke Bauters
  • Stefanie Belet
  • Jelle Verbeeck
  • Anna C. Jansen
  • Sara Seneca
  • Filip Roelens
  • Elfride De Baere
  • Peter Marynen
  • Guy Froyen
Original Investigation

Abstract

Xq28 microduplications of MECP2 are a prominent cause of a severe syndromic form of intellectual disability (ID) in males. Females are usually unaffected through near to complete X-inactivation of the aberrant X chromosome (skewing). In rare cases, affected females have been described due to random X-inactivation. Here, we report on two female patients carrying de novo MECP2 microduplications on their fully active X chromosomes. Both patients present with ID and additional clinical features. Mono-allelic expression confirmed complete skewing of X-inactivation. Consequently, significantly enhanced MECP2 mRNA levels were observed. We hypothesize that the cause for the complete skewing is due to a more harmful mutation on the other X chromosome, thereby forcing the MECP2 duplication to become active. However, we could not unequivocally identify such a second mutation by array-CGH or exome sequencing. Our data underline that, like in males, increased MECP2 dosage in females can contribute to ID too, which should be taken into account in diagnostics.

Supplementary material

439_2014_1469_MOESM1_ESM.pdf (802 kb)
Supplementary material 1 (PDF 802 kb)
439_2014_1469_MOESM2_ESM.pdf (313 kb)
Supplementary material 2 (PDF 313 kb)
439_2014_1469_MOESM3_ESM.pdf (376 kb)
Supplementary material 3 (PDF 376 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Nathalie Fieremans
    • 1
    • 2
  • Marijke Bauters
    • 1
    • 2
  • Stefanie Belet
    • 1
    • 2
  • Jelle Verbeeck
    • 1
    • 2
  • Anna C. Jansen
    • 3
  • Sara Seneca
    • 4
  • Filip Roelens
    • 5
  • Elfride De Baere
    • 6
  • Peter Marynen
    • 2
  • Guy Froyen
    • 1
    • 2
  1. 1.Human Genome LaboratoryVIB Center for the Biology of DiseaseLeuvenBelgium
  2. 2.Human Genome Laboratory, Department of Human GeneticsKU LeuvenLeuvenBelgium
  3. 3.Department of Pediatric NeurologyVrije Universiteit Brussel (VUB), UZ BrusselBrusselsBelgium
  4. 4.Center for Medical GeneticsVrije Universiteit Brussel (VUB), UZ BrusselBrusselsBelgium
  5. 5.Department of Pediatric NeurologyAZ DeltaRoeselareBelgium
  6. 6.Center for Medical GeneticsGhent University, Ghent University HospitalGhentBelgium

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