背景:BCOR基因的致病变异已在X连锁隐性隐性小眼症男性和X连锁显性眼心综合征(OFCD)女性中被鉴定。后一种情况以前被认为是罕见的,但近年来基因检测的增加导致了更多患者的鉴定。
方法:我们报告了来自5个家族的10例致病性BCOR变异患者的临床和分子研究结果。所有这些都是在两年的时间里在一个机构中看到的。
结果:我们强调该队列中的表型变异性和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的发生。
结论:在本报告中,我们证明了与OFCD表型相关的BCOR中四个新发现的变异体的新发现,并表明这种情况在患有先天性白内障的女性中的频率,包括单侧白内障,比预期的更常见。我们证明了筛查先天性白内障遗传原因的实用性。尽管以前曾报道过OFCD的性腺镶嵌现象,我们证明了体细胞镶嵌的存在,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。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.