A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome
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-o...
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2021
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oai:doaj.org-article:01e95e3556b74eb9b9985d9b000e849b2021-11-28T12:05:57ZA novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome10.1186/s12920-021-01130-71755-8794https://doaj.org/article/01e95e3556b74eb9b9985d9b000e849b2021-11-01T00:00:00Zhttps://doi.org/10.1186/s12920-021-01130-7https://doaj.org/toc/1755-8794Abstract 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.Rui WangWei-Qian WangXiao-Qin LiJuan ZhaoKun YangYong FengMeng-Meng GuoMin LiuXing LiuXi WangYong-Yi YuanXue GaoJin-Cao XuBMCarticleFOXC1Whole exome sequencingAxenfeld-Rieger syndromeInternal medicineRC31-1245GeneticsQH426-470ENBMC Medical Genomics, Vol 14, Iss 1, Pp 1-9 (2021) |
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DOAJ |
| language |
EN |
| topic |
FOXC1 Whole exome sequencing Axenfeld-Rieger syndrome Internal medicine RC31-1245 Genetics QH426-470 |
| spellingShingle |
FOXC1 Whole exome sequencing Axenfeld-Rieger syndrome Internal medicine RC31-1245 Genetics QH426-470 Rui Wang Wei-Qian Wang Xiao-Qin Li Juan Zhao Kun Yang Yong Feng Meng-Meng Guo Min Liu Xing Liu Xi Wang Yong-Yi Yuan Xue Gao Jin-Cao Xu A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome |
| description |
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. |
| format |
article |
| author |
Rui Wang Wei-Qian Wang Xiao-Qin Li Juan Zhao Kun Yang Yong Feng Meng-Meng Guo Min Liu Xing Liu Xi Wang Yong-Yi Yuan Xue Gao Jin-Cao Xu |
| author_facet |
Rui Wang Wei-Qian Wang Xiao-Qin Li Juan Zhao Kun Yang Yong Feng Meng-Meng Guo Min Liu Xing Liu Xi Wang Yong-Yi Yuan Xue Gao Jin-Cao Xu |
| author_sort |
Rui Wang |
| title |
A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome |
| title_short |
A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome |
| title_full |
A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome |
| title_fullStr |
A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome |
| title_full_unstemmed |
A novel variant in FOXC1 associated with atypical Axenfeld-Rieger syndrome |
| title_sort |
novel variant in foxc1 associated with atypical axenfeld-rieger syndrome |
| publisher |
BMC |
| publishDate |
2021 |
| url |
https://doaj.org/article/01e95e3556b74eb9b9985d9b000e849b |
| work_keys_str_mv |
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