title: Homozygous MED25 mutation implicated in eye-intellectual disability syndrome.
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.
authors: Pediatric Genetics Unit, Schneider Children's Medical Center of Israel, Petach Tikva, Israel, basel@post.tau.ac.il.
authors: Lina
authors: L
authors: Basel-Vanagaite
authors: Pola
authors: P
authors: Smirin-Yosef
authors: Jenna Lee
authors: JL
authors: Essakow
authors: Shay
authors: S
authors: Tzur
authors: Irina
authors: I
authors: Lagovsky
authors: Idit
authors: I
authors: Maya
authors: Metsada
authors: M
authors: Pasmanik-Chor
authors: Adva
authors: A
authors: Yeheskel
authors: Osnat
authors: O
authors: Konen
authors: Naama
authors: N
authors: Orenstein
authors: Monika
authors: M
authors: Weisz Hubshman
authors: Valerie
authors: V
authors: Drasinover
authors: Nurit
authors: N
authors: Magal
authors: Gaby
authors: G
authors: Peretz Amit
authors: Yael
authors: Y
authors: Zalzstein
authors: Avraham
authors: A
authors: Zeharia
authors: Mordechai
authors: M
authors: Shohat
authors: Rachel
authors: R
authors: Straussberg
authors: Didier
authors: D
authors: Monté
authors: Mali
authors: M
authors: Salmon-Divon
authors: Doron M
authors: DM
authors: Behar
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000293:Adolescent; D000818:Animals; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D005124:Eye Abnormalities / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D056892:Mediator Complex / Q000235:genetics* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D013577:Syndrome
chemical_list: C483045:MED25 protein, human; D056892:Mediator Complex; D012319:RNA Polymerase II