BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects

Hilton, Emma; Johnston, Jennifer J.; Whalen, Sandra; Okamoto, Nobuhiko; Hatsukawa, Yoshikazu; Nishio, Juntaro; Kohara, Hiroshi; Hirano, Yoshiko; Mizuno, Seiji; Torii, Chiharu; Kosaki, Kenjiro; Manouvrier, Sylvie; Boute, Odile; Perveen, Rahat; Law, Caroline; Moore, Anthony T.; FitzPatrick, David R.; Lemke, Johannes R.; Fellmann, Florence; Debray, François-Guillaume; Dastot-Le-Moal, Florence; Gérard, Marion; Martin, Josiane; Bitoun, Pierre; Goossens, Michel; Verloes, Alain; Schinzel, Albert; Bartholdi, Deborah; Bardakjian, Tanya; Hay, Beverly N.; Kim, Jenny; Johnston, Kylie; Lyons, Michael J.; Belmont, John W.; Biesecker, Leslie G.; Giurgea, Irina; Black, Graeme C M

doi:10.1038/ejhg.2009.52

Cited by 86 publications

(105 citation statements)

References 37 publications

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“…23 Most carrier females of IL1RAPL1 mutations and the carrier mother of the microduplication involving IL1RAPL1 showed normal intelligence. [23][24][25] In this study, one of the three affected females (MC18) had learning difficulties at school, which could be mild presentation of MR. As 18% of patients with BCOR mutations showed MR, 6 it is reasonable that the BCOR mutation, rather than IL1RAPL1 rearrangement, causes mild MR in MC18. Skewed and random X-inactivation in the mother (MC17b) and the elder daughter (MC17) was confirmed, respectively, in this family.…”

Section: Resultsmentioning

confidence: 99%

“…3 BCOR/Bcor is ubiquitously expressed in human tissues and is strongly and specifically expressed in the eye, brain, neural tube and branchial arches during mouse embryonic development, which are affected in OFCD. 4,5 In 2009, Hilton et al 6 clinically reviewed 35 cases with BCOR mutations and summarized the frequency of phenotypes: congenital cataract (100%), microphthalmia and/or microcornea (82%), facial dysmorphism (96%) including long narrow face and high nasal bridge, cardiac anomalies (74%, commonly septal defects), dental abnormalities (100%) such as delayed and/or primary dentition, root radiculomegaly, and absent/duplicated/fused teeth and mental retardation (18%). 6 Additionally, skeletal abnormalities such as 2nd-3rd toe syndactyly, hammer toes, and radioulnar synostosis are also observed in 97% patients.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 In 2009, Hilton et al 6 clinically reviewed 35 cases with BCOR mutations and summarized the frequency of phenotypes: congenital cataract (100%), microphthalmia and/or microcornea (82%), facial dysmorphism (96%) including long narrow face and high nasal bridge, cardiac anomalies (74%, commonly septal defects), dental abnormalities (100%) such as delayed and/or primary dentition, root radiculomegaly, and absent/duplicated/fused teeth and mental retardation (18%). 6 Additionally, skeletal abnormalities such as 2nd-3rd toe syndactyly, hammer toes, and radioulnar synostosis are also observed in 97% patients. Various types of mutations in BCOR have been described including nonsense, small insertions or deletions and splice site mutations, suggesting that the loss of functions (null allele) might result in OFCD.…”

Section: Introductionmentioning

confidence: 99%

“…Most mutations predicted to generate premature stop codons, likely suffering from nonsense-mediated mRNA decay, although nonsense-mediated mRNA decay was unable to be confirmed because of the severe skewed X-inactivation in blood leukocytes. 3,6 Nance-Horan syndrome (NHS) is an X-linked cataract-dental syndrome (MIM #302350) characterized by congenital cataract, dental abnormalities, facial dysmorphism and mental retardation. 7 Congenital cataract in affected male usually requires early surgery.…”

Section: Introductionmentioning

confidence: 99%

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A family of oculofaciocardiodental syndrome (OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS

et al. 2012

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A family of oculofaciocardiodental syndrome (OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS

et al. 2012

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“…2A, lower lane; refs. 16,17). In addition, p.P85L missense mutation in BCOR was identified in 2 patients with Lenz microphthalmia syndrome (16,17).…”

Section: Germline Bcor Mutations In Ofcd and Lenz Microphthalmia Syndmentioning

confidence: 99%

Clarifying the Impact of Polycomb Complex Component Disruption in Human Cancers

Yamamoto

Abe

Emi

2014

Molecular Cancer Research

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The dysregulation of proper transcriptional control is a major cause of developmental diseases and cancers. Polycomb proteins form chromatin-modifying complexes that transcriptionally silence genome regions in higher eukaryotes. The BCL6 corepressor (BCOR) complex comprises ring finger protein 1B (RNF2/RING1B), polycomb group ring finger 1 (PCGF1), and lysine-specific demethylase 2B (KDM2B) and is uniquely recruited to nonmethylated CpG islands, where it removes histone H3K36me2 and induces repressive histone H2A monoubiquitylation. Germline BCOR mutations have been detected in patients with oculofaciocardiodental and Lenz microphthalmia syndromes, which are inherited conditions. Recently, several variants of BCOR and BCORlike 1 (BCORL1) chimeric fusion transcripts were reported in human cancers, including acute promyelocytic leukemia, bone sarcoma, and hepatocellular carcinoma. In addition, massively parallel sequencing has identified inactivating somatic BCOR and BCORL1 mutations in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia, medulloblastoma, and retinoblastoma. More importantly, patients with AML and MDS with BCOR mutations exhibit poor prognosis. This perspective highlights the detection of BCOR mutations and fusion transcripts of BCOR and BCORL1 and discusses their importance for diagnosing cancer subtypes and estimating the treatment responses of patients. Furthermore, this perspective proposes the need for additional functional studies to clarify the oncogenic mechanism by which BCOR and BCORL1 are disrupted in cancers, and how this may lead to the development of novel therapeutics. Mol Cancer Res; 12(4); 479-84. Ó2014 AACR. IntroductionA major cause of developmental diseases and cancers is the dysregulation of proper transcriptional control, a process that is directly regulated by transcription factors, coactivators, and corepressors. Till date, several hundred transcriptional coregulators have been reported in the literature. Recently, the increased use of massively parallel sequencing techniques has expanded our knowledge on the induction of congenital diseases and cancers caused by specific gene mutations.

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Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract

et al. 2021

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population-based differences in genotype and phenotype heterogeneity are important for targeted and patient-specific diagnosis and treatment, counseling, and screening strategies.OBJECTIVE To report disease-causing variants and their detailed phenotype in patients with bilateral congenital cataract from a single center in Switzerland and thereby draw a genetic map and perform a genotype-phenotype comparison of this cohort.DESIGN, SETTING, AND PARTICIPANTS This clinical and molecular-genetic cohort study took place through the collaboration of the

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BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects

Cited by 86 publications

References 37 publications

A family of oculofaciocardiodental syndrome (OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS

A family of oculofaciocardiodental syndrome (OFCD) with a novel BCOR mutation and genomic rearrangements involving NHS

Clarifying the Impact of Polycomb Complex Component Disruption in Human Cancers

Genetic Analysis in a Swiss Cohort of Bilateral Congenital Cataract

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