Oculo-facio-cardio-dental syndrome in three succeeding generations: genotypic data and phenotypic features

Abstract

Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked disorder mainly manifesting in females. Patients show ocular, facial, cardiac, and dental abnormalities. OFCD syndrome is caused by heterozygous mutations in the BCOR gene, located in Xp11.4, encoding the BCL6 co-repressor. We report a Croatian family with four female members (grandmother, mother and monozygotic female twins) diagnosed with OFCD syndrome who carry the novel BCOR mutation c.4438C>T (p.R1480*). They present high intrafamilial phenotypic variability with special regard to cardiac defect and cataract that showed more severe disease expression in successive generations. Clinical and radiographic examination of the mother of the twins revealed a talon cusp involving the permanent maxillary right central incisor. This is the first known report of a talon cusp in OFCD syndrome with a novel mutation in the BCOR gene.

Identification of nuclear localization signals within the human BCOR protein

“…The reported mutations were dispersed along the entire 15 exons of the BCOR gene and most of these mutations were predicted to generate premature stop codons (PTCs). Regardless of the mutation site, all patients have similar typical OFCD phenotypes, but differ in severity even in single families with the same mutation[8].…”

Oculo-facio-cardio-dental (OFCD) syndrome: The first Italian case of BCOR and co-occurring OTC gene deletion

“…The infant shows square face, broad forehead, eyebrows laterally extended and horizontal, and wide nasal bridge with broad nasal tip and deep. The phenotypic difference between adult and infant is important in syndromic conditions with mild phenotype in younger patients (Lozić et al, 2012). Moreover, the most important criteria for the diagnosis of oculo-facio-cardio-dental syndrome are dental anomalies, in particular extreme elongation of the cuspids' roots, but only in permanent dentition.…”

Review Recent progress in identification and characterization of loci associated with sex-linked congenital cataract

“…The protein selectively interacts with the POZ domain of BCL6. BCOR is expressed in many tissues, including the eyes, teeth, and the nerve canal, and plays an important role in the regulation of early embryo development (Lozic et al, 2012).…”

“…Lozic et al (2012) reported a new heterozygous mutation, c.4438C>T (p.R1480*), in exon 11 of BCOR in identical twins with oculo-facio-cardio-dental syndrome by short tandem repeat analysis and sequencing. Danda et al (2014) identified a novel mutation in exon 7 of BCOR, c.3490C>T (p.R1164*), in two Indian sisters with oculo-faciocardio-dental syndrome, via sequencing.…”