Mutations in MED12 cause X-linked ohdo syndrome

Anneke T. Vulto-Van Silfhout, Bert B.A. De Vries, Bregje W.M. Van Bon, Alexander Hoischen, Martina Ruiterkamp-Versteeg, Christian Gilissen, Fangjian Gao, Marloes Van Zwam, Cornelis L. Harteveld, Anthonie J. Van Essen, Ben C.J. Hamel, Tjitske Kleefstra, Michèl A.A.P. Willemsen, Helger G. Yntema, Hans Van Bokhoven, Han G. Brunner, Thomas G. Boyer, Arjan P.M. De Brouwer

Research output: Contribution to journalArticlepeer-review

69 Scopus citations


Ohdo syndrome comprises a heterogeneous group of disorders characterized by intellectual disability (ID) and typical facial features, including blepharophimosis. Clinically, these blepharophimosis-ID syndromes have been classified in five distinct subgroups, including the Maat-Kievit-Brunner (MKB) type, which, in contrast to the others, is characterized by X-linked inheritance and facial coarsening at older age. We performed exome sequencing in two families, each with two affected males with Ohdo syndrome MKB type. In the two families, MED12 missense mutations (c.3443G>A [p.Arg1148His] or c.3493T>C [p.Ser1165Pro]) segregating with the phenotype were identified. Upon subsequent analysis of an additional cohort of nine simplex male individuals with Ohdo syndrome, one additional de novo missense change (c.5185C>A [p.His1729Asn]) in MED12 was detected. The occurrence of three different hemizygous missense mutations in three unrelated families affected by Ohdo syndrome MKB type shows that mutations in MED12 are the underlying cause of this X-linked form of Ohdo syndrome. Together with the recently described KAT6B mutations resulting in Ohdo syndrome Say/Barber/Biesecker/Young/Simpson type, our findings point to aberrant chromatin modification as being central to the pathogenesis of Ohdo syndrome.

Original languageEnglish (US)
Pages (from-to)401-406
Number of pages6
JournalAmerican Journal of Human Genetics
Issue number3
StatePublished - Mar 7 2013

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Mutations in MED12 cause X-linked ohdo syndrome'. Together they form a unique fingerprint.

Cite this