BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects.
BCOR analysis in patients with OFCD and Lenz microphthalmia syndromes, mental retardation with ocular anomalies, and cardiac laterality defects.
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DOI：
10.1038/ejhg.2009.52
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发表时间：
2009-10
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影响因子：
--
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中科院分区：
文献类型：
--
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眼面心齿（OFCD）和Lenz小眼综合征是x连锁小眼疾病谱系的一部分，其特征是眼睛、牙齿、心脏和骨骼异常以及智力迟钝。这两种综合征是等位基因，由BCL-6协同抑制因子（BCOR）突变引起。为了扩展与BCOR致病突变相关的表型系列，我们对以下患者的BCOR基因进行了测序：1)OFCD综合征；2)假定的x连锁（“Lenz”）小眼综合征；3)孤立性眼缺陷和4)偏侧表型。我们提出了一组新的女性OFCD综合征和BCOR零突变，支持BCOR是该综合征的唯一分子原因的假设。我们首次在两名患有OFCD综合征的女性和一名明显无症状的女性中发现了马赛克BCOR突变。我们报告了一名被诊断为孤立性眼部缺陷的女性，并确定了OFCD综合征的一些小特征，表明OFCD综合征可能是轻微的和未被诊断的。我们对一组被诊断为x连锁小眼的男性进行了测序，并在一个病例中发现了p.P85L突变，这表明BCOR突变并不是导致男性x连锁小眼的主要原因。在一组非特异性侧侧缺陷患者中没有BCOR突变，这表明BCOR突变不是孤立性心脏和侧侧缺陷的主要原因。OFCD和Lenz小眼综合征的表型分析表明，除了先天性白内障、小眼和神经根肥大的标准诊断标准外，患者还应检查骨骼缺陷，特别是尺桡关节闭锁和心脏/侧侧缺陷。
Oculofaciocardiodental (OFCD) and Lenz microphthalmia syndromes form part of a spectrum of X-linked microphthalmia disorders characterised by ocular, dental, cardiac and skeletal anomalies and mental retardation. The two syndromes are allelic, caused by mutations in the BCL-6 corepressor (BCOR). To extend the series of phenotypes associated with pathogenic mutations in BCOR, we sequenced the BCOR gene in patients with 1) OFCD syndrome 2) putative X-linked (“Lenz”) microphthalmia syndrome 3) isolated ocular defects and 4) laterality phenotypes. We present a new cohort of females with OFCD syndrome and null mutations in BCOR, supporting the hypothesis that BCOR is the sole molecular cause of this syndrome. We identify for the first time mosaic BCOR mutations in two females with OFCD syndrome and one apparently asymptomatic female. We present a female diagnosed with isolated ocular defects and identify minor features of OFCD syndrome, suggesting that OFCD syndrome may be mild and underdiagnosed. We have sequenced a cohort of males diagnosed with putative X-linked microphthalmia and found a mutation, p.P85L, in a single case, suggesting that BCOR mutations are not a major cause of X-linked microphthalmia in males. The absence of BCOR mutations in a panel of patients with non-specific laterality defects suggests that mutations in BCOR are not a major cause of isolated heart and laterality defects. Phenotypic analysis of OFCD and Lenz microphthalmia syndromes shows that in addition to the standard diagnostic criteria of congenital cataract, microphthalmia and radiculomegaly, patients should be examined for skeletal defects, particularly radioulnar synostosis, and cardiac/laterality defects.
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影响因子：
3.5
作者：
Hilton, Emma N.;Manson, Forbes D. C.;Black, Graeme C. M.
通讯作者：
Black, Graeme C. M.
DOI：
10.1002/ajmg.1330
发表时间：
2001-06-15
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
Lehman, DM;Sponsel, WE;Leach, RJ
通讯作者：
Leach, RJ
DOI：
10.1016/0030-4220(90)90025-n
发表时间：
1990-12-01
影响因子：
--
作者：
MARASHI, AH;GORLIN, RJ
通讯作者：
GORLIN, RJ
DOI：
10.1016/j.ijom.2006.05.001
发表时间：
2006-11-01
影响因子：
2.4
作者：
McGovern, E.;AL-Mudaffer, M.;Reardon, W.
通讯作者：
Reardon, W.
影响因子：
4
作者：
Niel, F;Martin, J;Girodon, E
通讯作者：
Girodon, E