A family of oculofaciocardiodental syndrome (OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS.
Oculofaciocardiodental syndrome (OFCD) is an X-linked dominant disorder associated with male lethality, presenting with congenital cataract, dysmorphic face, dental abnormalities and septal heart defects. Mutations in BCOR (encoding BCL-6-interacting corepressor) cause OFCD. Here, we report on a Korean family with common features of OFCD including bilateral 2nd-3rd toe syndactyly and septal heart defects in three affected females (mother and two daughters). Through the mutation screening and copy number analysis using genomic microarray, we identified a novel heterozygous mutation, c.888delG, in the BCOR gene and two interstitial microduplications at Xp22.2-22.13 and Xp21.3 in all the three affected females. The BCOR mutation may lead to a premature stop codon (p.N297IfsX80). The duplication at Xp22.2-22.13 involved the NHS gene causative for Nance-Horan syndrome, which is an X-linked disorder showing similar clinical features with OFCD in affected males, and in carrier females with milder presentation. Considering the presence of bilateral 2nd-3rd toe syndactyly and septal heart defects, which is unique to OFCD, the mutation in BCOR is likely to be the major determinant for the phenotypes in this family.
Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Yukiko
Y
Kondo
Hirotomo
H
Saitsu
Toshinobu
T
Miyamoto
Kiyomi
K
Nishiyama
Yoshinori
Y
Tsurusaki
Hiroshi
H
Doi
Noriko
N
Miyake
Na-Kyung
NK
Ryoo
Jeong Hun
JH
Kim
Young Suk
YS
Yu
Naomichi
N
Matsumoto
D000328:Adult; D001483:Base Sequence; D001921:Brain / Q000002:abnormalities; D002386:Cataract / Q000175:diagnosis / Q000235:genetics* / Q000151:congenital; D002648:Child; D056905:Chromosome Breakpoints; D056915:DNA Copy Number Variations; D005260:Female; D023061:Gene Order; D006239:Haplotypes; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000235:genetics*; D006343:Heart Septal Defects; D006579:Heterozygote; D006801:Humans; D008565:Membrane Proteins; D008850:Microphthalmos / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D010375:Pedigree; D020033:Protein Isoforms / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D014178:Translocation, Genetic; D049951:X Chromosome Inactivation
C411984:BCOR protein, human; D008565:Membrane Proteins; C488621:NHS protein, human; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins