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

Nathalie Fieremans, M. Bauters, Stefanie Belet, Jelle Verbeeck, Anna Jansen, Sara Seneca, Filip Roelens, Elfride De Baere, P. Marynen, G. Froyen

Onderzoeksoutput: Articlepeer review

18 Citaten (Scopus)

Samenvatting

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.
Originele taal-2English
Pagina's (van-tot)1359-1367
Aantal pagina's9
TijdschriftHuman Genetics
Volume133
Nummer van het tijdschrift11
DOI's
StatusPublished - 2014

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