1. ¹Institut für Medizinische Genetik, Charité, Campus Virchow-Klinikum, Berlin, Germany
2. ²Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany
3. ³Praxis für Pränatale Diagnostik und Humangenetik, Hamburg, Germany
4. ⁴Institut für Klinische Genetik, Medizinische Fakultät Carl Gustav Carus der TU Dresden, Dresden, Germany
5. ⁵Zentrum für Kinder- und Jugendmedizin, Klinikum Oldenburg, Oldenburg, Germany
6. ⁶Medizinische Genetik, Universitätsklinikum Tübingen, Germany
7. ⁷Medizinische Genetik, Kinderzentrum München, München, Germany
8. ⁸Institut für Humangenetik, Universitätsklinikum Essen, Essen, Germany

Correspondence: Dr K Kutsche, Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Butenfeld 42, D-22529 Hamburg, Germany. Tel: +49 40 42803 4597; Fax: +49 40 42803 5138; E-mail: kkutsche@uke.uni-hamburg.de

⁹These authors contributed equally to this work.

¹⁰Current address: Institut für Humangenetik, Universität zu Köln, Germany.

Received 5 November 2004; Revised 24 January 2005; Accepted 25 January 2005; Published online 16 March 2005.

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.