title: Novel mutations in BCOR in three patients with oculo-facio-cardio-dental syndrome, but none in Lenz microphthalmia syndrome.
abstract: Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked dominant condition with male lethality characterized by microphthalmia, congenital cataracts, facial dysmorphic features, congenital heart defects, and dental anomalies. Mutations in BCOR (BCL6 co-repressor) located in Xp11.4 have been described to cause OFCD syndrome. Lenz microphthalmia syndrome is inherited in an X-linked recessive pattern comprising microphthalmia/anophthalmia, mental retardation, malformed ears, digital, skeletal, and urogenital anomalies (synonym: microphthalmia with associated anomalies (MAA)). One locus for MAA has been mapped to Xq27-q28. Nonetheless, linkage and subsequent mutation analysis revealed a single missense mutation (p.P85L) in BCOR in a large family with presumed Lenz microphthalmia syndrome (MAA2). We describe novel mutations in BCOR in three patients with OFCD syndrome, two small deletions (c.2488_2489delAG and c.3286delG) and a submicroscopic deletion of about 60 kb encompassing at least BCOR exons 2-15. No BCOR mutation was detected in eight patients with Lenz microphthalmia syndrome. Our data confirm that BCOR is the causative gene for OFCD syndrome; however, the failure to identify any mutation in patients with Lenz microphthalmia syndrome together with the oligosymptomatic phenotype in the reported MAA2 patients suggest that BCOR is not the major gene for this syndrome.
authors.affiliation: Institut für Medizinische Genetik, Charité, Campus Virchow-Klinikum, Berlin, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Horn
authors.forename: Magdalena
authors.initials: M
authors.lastname: Chyrek
authors.forename: Saskia
authors.initials: S
authors.lastname: Kleier
authors.forename: Sabine
authors.initials: S
authors.lastname: Lüttgen
authors.forename: Hanno
authors.initials: H
authors.lastname: Bolz
authors.forename: Georg-Klaus
authors.initials: GK
authors.lastname: Hinkel
authors.forename: Georg Christoph
authors.initials: GC
authors.lastname: Korenke
authors.forename: Angelika
authors.initials: A
authors.lastname: Riess
authors.forename: Can
authors.initials: C
authors.lastname: Schell-Apacik
authors.forename: Sigrid
authors.initials: S
authors.lastname: Tinschert
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.forename: Gabriele
authors.initials: G
authors.lastname: Gillessen-Kaesbach
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kutsche
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000293:Adolescent; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics; D004252:DNA Mutational Analysis; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006330:Heart Defects, Congenital / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D008850:Microphthalmos / Q000235:genetics*; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: C411984:BCOR protein, human; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins