Redwood A, Douzgou S, Waller S, Ramsden S, Roberts A, Bonin H, Lloyd I C, Ashworth J, Black G C M, Clayton-Smith J
University of Manchester Medical School, Manchester, United Kingdom.
Manchester Centre For Genomic Medicine, St Mary's Hospital, Manchester and University Hospitals NHS Foundation Trust Manchester Academic Health Sciences Centre, United Kingdom.
Eur J Med Genet. 2020 Feb;63(2):103658. doi: 10.1016/j.ejmg.2019.04.015. Epub 2019 Apr 30.
Pathogenic variants in the BCOR gene have been identified in males with X-linked recessive microphthalmia and in females with X-linked dominant oculofaciocardiodental (OFCD) syndrome. This latter condition has previously been regarded as rare but the increased availability of genetic testing in recent years has led to the identification of a greater number of patients.
We report the clinical and molecular findings in a series of 10 patients with pathogenic BCOR variants from 5 families, all seen in a single institution over a two year period.
We emphasize the phenotypic variability in this cohort and the diverse genetic mechanisms involved which included point mutations and deletions of BCOR as well as the occurrence of gonadal and somatic mosaicism.
In this report we demonstrate the novel findings of four newly identified variants in BCOR associated with an OFCD phenotype, and suggest that the frequency of this condition in females presenting with congenital cataract, including unilateral cataract, is more common than anticipated. We demonstrate the utility of screening for genetic causes of congenital cataract. Although gonadal mosaicism in OFCD had previously been reported, we demonstrate the presence of somatic mosaicism where BCOR mutations may only be detected in DNA from tissues other than blood such as buccal cells.
已在患有X连锁隐性小眼症的男性以及患有X连锁显性眼面心脏牙本质（OFCD）综合征的女性中发现BCOR基因的致病变异。后一种疾病以前被认为很罕见，但近年来基因检测的可及性增加导致发现了更多患者。
我们报告了来自5个家庭的10例携带BCOR致病变异患者的临床和分子学发现，所有这些患者均在两年内在单一机构就诊。
我们强调了该队列中的表型变异性以及所涉及的多种遗传机制，包括BCOR的点突变和缺失以及性腺和体细胞镶嵌现象的发生。
在本报告中，我们展示了与OFCD表型相关的BCOR中四个新发现变异的新发现，并表明在患有先天性白内障（包括单侧白内障）的女性中，这种疾病的发生率比预期的更常见。我们证明了筛查先天性白内障遗传病因的实用性。虽然之前已报道过OFCD中的性腺镶嵌现象，但我们证明了体细胞镶嵌现象的存在，其中BCOR突变可能仅在血液以外的组织（如颊细胞）的DNA中检测到。
