PDF(Pubmed)
Abstract：
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.
摘要：
叉头框C1（FOXC1）的突变已知会导致常染色体显性遗传性Axenfeld-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和缺乏典型表现，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5岁男孩在FOXC1中的致病性框架内变异，该男孩表现为过度端粒，双眼瞳孔变形，传导性听力损失,牙齿缺陷。通过整个外显子组测序，我们在FOXC1中鉴定出3bp的缺失，c.516_518delGCG（p。Arg173del）作为致病变体，这是从头到尾的，在父母中没有发现，根据美国医学遗传学和基因组学学会指南，可以归类为“致病变异”。在确认此FOXC1变体后，收集并分析Axenfeld-Rieger综合征相关临床特征的临床资料.此外，虽然受影响的个体存在听力损失，然而,听力损失是传导性的，在随访期间是可逆的，这可能与FOXC1变体无关，并且是巧合。FOXC1的常规检查对于听力亢进相关综合征的遗传诊断是必要的。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。
