A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome
Abstract Background Treacher Collins syndrome (TCS; OMIM 154500) is a craniofacial developmental disorder. Methods To investigate the genetic features of a four-generation Chinese family with TCS, clinical examinations, hearing tests, computed tomography, whole-exome sequencing (WES), Sanger sequenc...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-024-01828-4 |
| _version_ | 1797246936578785280 |
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| author | Haojie Sun Xinda Xu Binjun Chen Yanmei Wang Jihan Lyu Luo Guo Yasheng Yuan Dongdong Ren |
| author_facet | Haojie Sun Xinda Xu Binjun Chen Yanmei Wang Jihan Lyu Luo Guo Yasheng Yuan Dongdong Ren |
| author_sort | Haojie Sun |
| collection | DOAJ |
| description | Abstract Background Treacher Collins syndrome (TCS; OMIM 154500) is a craniofacial developmental disorder. Methods To investigate the genetic features of a four-generation Chinese family with TCS, clinical examinations, hearing tests, computed tomography, whole-exome sequencing (WES), Sanger sequencing, reverse transcription (RT)-PCR, and the Minigene assay were performed. Results The probands, an 11-year-old male and his cousin exhibited typical clinical manifestations of TCS including conductive hearing loss, downward slanting palpebral fissures, and mandibular hypoplasia. Computed tomography revealed bilateral fusion of the anterior and posterior stapedial crura and malformation of the long crura of the incus. WES of both patients revealed a novel heterozygous intronic variant, i.e., c.4342 + 5_4342 + 8delGTGA (NM_001371623.1) in TCOF1. Minigene expression analysis revealed that the c.4342 + 5_4342 + 8delGTGA variant in TCOF1 caused a partial deletion of exon 24 (c.4115_4342del: p.Gly1373_Arg1448del), which was predicted to yield a truncated protein. The deletion was further confirmed via RT-PCR and sequencing of DNA from proband blood cells. A heterozygous variant in the POLR1C gene (NM_203290; exon6; c.525delG) was found almost co-segregated with the TCOF1 pathogenic variant. Conclusions In conclusion, we identified a heterozygous TCOF1 splicing variant c.4342 + 5_4342 + 8delGTGA (splicing) in a Chinese TSC family with ossicular chain malformations and facial anomalies. Our findings broadened the spectrum of TCS variants and will facilitate diagnostics and prognostic predictions. |
| first_indexed | 2024-04-24T19:50:43Z |
| format | Article |
| id | doaj.art-753d9fde57094c8cb74b9258daf5fb95 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-04-24T19:50:43Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-753d9fde57094c8cb74b9258daf5fb952024-03-24T12:36:43ZengBMCBMC Medical Genomics1755-87942024-03-0117111010.1186/s12920-024-01828-4A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndromeHaojie Sun0Xinda Xu1Binjun Chen2Yanmei Wang3Jihan Lyu4Luo Guo5Yasheng Yuan6Dongdong Ren7Department of Otorhinolaryngology, ENT Institute, Eye and ENT Hospital, Fudan UniversityDepartment of Otorhinolaryngology, ENT Institute, Eye and ENT Hospital, Fudan UniversityDepartment of Otorhinolaryngology, ENT Institute, Eye and ENT Hospital, Fudan UniversityDepartment of Otorhinolaryngology, ENT Institute, Eye and ENT Hospital, Fudan UniversityDepartment of Otorhinolaryngology, ENT Institute, Eye and ENT Hospital, Fudan UniversityNHC Key Laboratory of Hearing Medicine, Fudan UniversityDepartment of Otorhinolaryngology, ENT Institute, Eye and ENT Hospital, Fudan UniversityDepartment of Otorhinolaryngology, ENT Institute, Eye and ENT Hospital, Fudan UniversityAbstract Background Treacher Collins syndrome (TCS; OMIM 154500) is a craniofacial developmental disorder. Methods To investigate the genetic features of a four-generation Chinese family with TCS, clinical examinations, hearing tests, computed tomography, whole-exome sequencing (WES), Sanger sequencing, reverse transcription (RT)-PCR, and the Minigene assay were performed. Results The probands, an 11-year-old male and his cousin exhibited typical clinical manifestations of TCS including conductive hearing loss, downward slanting palpebral fissures, and mandibular hypoplasia. Computed tomography revealed bilateral fusion of the anterior and posterior stapedial crura and malformation of the long crura of the incus. WES of both patients revealed a novel heterozygous intronic variant, i.e., c.4342 + 5_4342 + 8delGTGA (NM_001371623.1) in TCOF1. Minigene expression analysis revealed that the c.4342 + 5_4342 + 8delGTGA variant in TCOF1 caused a partial deletion of exon 24 (c.4115_4342del: p.Gly1373_Arg1448del), which was predicted to yield a truncated protein. The deletion was further confirmed via RT-PCR and sequencing of DNA from proband blood cells. A heterozygous variant in the POLR1C gene (NM_203290; exon6; c.525delG) was found almost co-segregated with the TCOF1 pathogenic variant. Conclusions In conclusion, we identified a heterozygous TCOF1 splicing variant c.4342 + 5_4342 + 8delGTGA (splicing) in a Chinese TSC family with ossicular chain malformations and facial anomalies. Our findings broadened the spectrum of TCS variants and will facilitate diagnostics and prognostic predictions.https://doi.org/10.1186/s12920-024-01828-4Treacher Collins syndromeTCOF1Heterozygous variantsWhole-exome sequencingMinigeneOssicular chain malformation |
| spellingShingle | Haojie Sun Xinda Xu Binjun Chen Yanmei Wang Jihan Lyu Luo Guo Yasheng Yuan Dongdong Ren A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome BMC Medical Genomics Treacher Collins syndrome TCOF1 Heterozygous variants Whole-exome sequencing Minigene Ossicular chain malformation |
| title | A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome |
| title_full | A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome |
| title_fullStr | A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome |
| title_full_unstemmed | A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome |
| title_short | A novel intronic TCOF1 pathogenic variant in a Chinese family with Treacher Collins syndrome |
| title_sort | novel intronic tcof1 pathogenic variant in a chinese family with treacher collins syndrome |
| topic | Treacher Collins syndrome TCOF1 Heterozygous variants Whole-exome sequencing Minigene Ossicular chain malformation |
| url | https://doi.org/10.1186/s12920-024-01828-4 |
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