A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome.
A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome.
复制标题
FOXC1 中的一种新变异与非典型 Axenfeld-Rieger 综合征相关。
DOI：
10.1186/s12920-021-01130-7
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发表时间：
2021-11-22
影响因子：
2.7
通讯作者：
Xu JC
中科院分区：
文献类型：
--
作者：
Wang R;Wang WQ;Li XQ;Zhao J;Yang K;Feng Y;Guo MM;Liu M;Liu X;Wang X;Yuan YY;Gao X;Xu JC
已知叉头盒C1（FOXC 1）中的突变引起常染色体显性遗传性Axenovirus-Rieger综合征，这是一种以眼部和全身特征为特征的遗传性疾病，包括青光眼、可变牙齿缺陷、颅面畸形和听力损失。由于眼部疾病的迟发性和缺乏典型的表现，临床诊断提出了巨大的挑战。在这项研究中，我们描述了一个致病的帧内变异FOXC 1在一个5岁的男孩谁是提出了间距过宽，瞳孔变形，双眼，传导性听力损失，和牙齿缺陷。通过全外显子组测序，我们确定FOXC 1，c.516_518delGCG（p.Arg173del）中的一个3 bp缺失为致病变异，该变异为新发变异，在父母中未检测到，根据美国医学遗传学和基因组学学会指南，可将其归类为“致病变异”。在确认这种FOXC 1变体后，收集并分析了Axenovirus-Rieger综合征相关临床特征的临床数据。此外，虽然受影响的个体存在听力损失，但是，听力损失是传导性的，并且在随访期间是可逆的，这可能与FOXC 1变异无关，而是巧合。FOXC 1的常规检测对于远距扩增相关综合征的基因诊断是必要的。这些发现可能有助于临床医生达到正确的临床和分子诊断，并提供适当的遗传咨询。在线版本包含补充材料，可通过10.1186/s12920-021-01130-7获得。
Mutations in the Forkhead Box C1 (FOXC1) are known to cause autosomal dominant hereditary Axenfeld-Rieger syndrome, which is a genetic disorder characterized by ocular and systemic features including glaucoma, variable dental defects, craniofacial dysmorphism and hearing loss. Due to late-onset of ocular disorders and lack of typical presentation, clinical diagnosis presents a huge challenge. In this study, we described a pathogenic in-frame variant in FOXC1 in one 5-year-old boy who is presented with hypertelorism, pupil deformation in both eyes, conductive hearing loss, and dental defects. By whole exome sequencing, we identified a 3 bp deletion in FOXC1, c.516_518delGCG (p.Arg173del) as the disease-causing variant, which was de novo and not detected in the parents, and could be classified as a “pathogenic variant” according to the American College of Medical Genetics and Genomics guidelines. After confirmation of this FOXC1 variant, clinical data on Axenfeld-Rieger syndrome-associated clinical features were collected and analyzed. Furthermore, Although the affected individual present hearing loss, however, the hearing loss is conductive and is reversible during the follow-up, which might not linke to the FOXC1 variant and is coincidental. Routine examination of FOXC1 is necessary for the genetic diagnosis of hypertelorism-associated syndrome. These findings may assist clinicians in reaching correct clinical and molecular diagnoses, and providing appropriate genetic counseling. The online version contains supplementary material available at 10.1186/s12920-021-01130-7.
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