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Web End = Hum Genet (2015) 134:577587 DOI 10.1007/s00439-015-1541-x
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Web End = Homozygous MED25 mutation implicated in eyeintellectual disability syndrome
Lina BaselVanagaite1,2,3,5 Pola SmirinYosef4,5 Jenna Lee Essakow2 Shay Tzur8 Irina Lagovsky2,5 Idit Maya3 Metsada PasmanikChor6 Adva Yeheskel6
Osnat Konen2,7 Naama Orenstein1,3 Monika Weisz Hubshman1,2,3
Valerie Drasinover3 Nurit Magal3 Gaby Peretz Amit3 Yael Zalzstein3 Avraham Zeharia2,9 Mordechai Shohat2,3,5 Rachel Straussberg11,1,2
Didier Mont10 Mali SalmonDivon4 Doron M. Behar3,8
Received: 20 December 2014 / Accepted: 11 March 2015 / Published online: 20 March 2015 Springer-Verlag Berlin Heidelberg 2015
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.
Introduction
The application of classical and high-throughput genomic technologies has led to the identication of a large number of genes involved in the pathogenesis of syndromes involving intellectual disability accompanied by eye and brain abnormalities. Examples of syndromes associated with both intellectual disability and congenital eye abnormalities include Warburg micro syndrome (MIM 600118, 614222, 615663, 614225), Kaufman oculocerebrofacial syndrome (MIM 244450), Cerebro-oculo-facio-skeletal syndrome
Abstract Genetic syndromes involving both brain and eye abnormalities are numerous and include syndromes such as Warburg micro syndrome, Kaufman oculocerebro-facial 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
L. Basel-Vanagaite and P. Smirin-Yosef are equally contributed and shares rst joint authorship.
Electronic supplementary material The online version of this article (doi:http://dx.doi.org/10.1007/s00439-015-1541-x
Web End =10.1007/s00439-015-1541-x ) contains supplementary material, which is available to authorized users.
* Lina Basel-Vanagaite [email protected]
1 Pediatric Genetics Unit, Schneider Childrens Medical Center of...