2. Academic Validation
  3. Homozygous MED25 mutation implicated in eye-intellectual disability syndrome

Homozygous MED25 mutation implicated in eye-intellectual disability syndrome

  • Hum Genet. 2015 Jun;134(6):577-87. doi: 10.1007/s00439-015-1541-x.
Lina Basel-Vanagaite 1,  Pola Smirin-Yosef,  Jenna Lee Essakow,  Shay Tzur,  Irina Lagovsky,  Idit Maya,  Metsada Pasmanik-Chor,  Adva Yeheskel,  Osnat Konen,  Naama Orenstein,  Monika Weisz Hubshman,  Valerie Drasinover,  Nurit Magal,  Gaby Peretz Amit,  Yael Zalzstein,  Avraham Zeharia,  Mordechai Shohat,  Rachel Straussberg,  Didier Monté,  Mali Salmon-Divon,  Doron M Behar
Affiliations

Affiliation

  • 1 Pediatric Genetics Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel, basel@post.tau.ac.il.
PMID: 25792360 DOI: 10.1007/s00439-015-1541-x
Abstract

Genetic syndromes involving both brain and eye abnormalities are numerous and include syndromes such as Warburg micro syndrome, Kaufman oculocerebrofacial syndrome, Cerebro-oculo-facio-skeletal syndrome, Kahrizi syndrome and Others. Using exome Sequencing, we have been able to identify homozygous mutation p.(Tyr39Cys) in MED25 as the cause of a syndrome characterized by eye, brain, cardiac and palatal abnormalities as well as growth retardation, microcephaly and severe intellectual disability in seven patients from four unrelated families, all originating from the same village. The protein encoded by MED25 belongs to Mediator complex or MED complex, which is an evolutionary conserved multi-subunit RNA polymerase II transcriptional regulator complex. The MED25 point mutation is located in the von Willebrand factor type A (MED25 VWA) domain which is responsible for MED25 recruitment into the Mediator complex; co-immunoprecipitation experiment demonstrated that this mutation dramatically impairs MED25 interaction with the Mediator complex in mammalian cells.

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