Dan-Yan Zhuang, Shu-Ni Sun, Zhuo-Jie Hu, Min Xie, Yu-Xin Zhang, Lu-Lu Yan, Jie-Wen Pan, Hai-Bo Li
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The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing.</p><p><strong>Results: </strong>Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before.</p><p><strong>Conclusion: </strong>Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.</p>","PeriodicalId":18852,"journal":{"name":"Molecular Genetics & Genomic Medicine","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10915472/pdf/","citationCount":"0","resultStr":"{\"title\":\"Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome.\",\"authors\":\"Dan-Yan Zhuang, Shu-Ni Sun, Zhuo-Jie Hu, Min Xie, Yu-Xin Zhang, Lu-Lu Yan, Jie-Wen Pan, Hai-Bo Li\",\"doi\":\"10.1002/mgg3.2405\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology.</p><p><strong>Methods: </strong>The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing.</p><p><strong>Results: </strong>Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before.</p><p><strong>Conclusion: </strong>Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. 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引用次数: 0
摘要
背景:特雷撤-科林斯Ι综合征(TCS1,OMIM:154500)是一种常染色体显性遗传病,具有眼耳畸形、小颌畸形、唇裂等颅面发育不良以及反复呼吸道感染和传导性听力损失等一系列临床表现。文章报告了两例特雷撤-科林斯综合征患者的临床特征、基因变异和病因:方法:回顾性分析了两名由TCOF1基因变异引起的特雷撤-科林斯综合征患者的临床资料。通过全外显子组测序(WES)检测患者TCOF1基因的致病变异,并通过Sanger测序对变异进行验证:Proband 1 患有双侧颅面畸形、传导性听力损失和反复呼吸道感染。Proband 2 患有双侧颅面畸形和腭裂,在其家族中也有类似表现。她出生后不久就因呼吸困难和喂养困难而死亡。WES 在两名疑似患者中发现了两个 TCOF1 基因的新型致病变异体,每个变异体都有一个。根据美国医学遗传学和基因组学学院(American College of Medical Genetics and Genomics)的研究,在 Proband 1 中检测到 TCOF1 基因的杂合变异 NM_001371623.1:c.877del (p. Ala293Profs*34),该变异被评估为可能致病(LP)和新变异。在 Proband 2 中发现的另一个变异是 NM_001135243.1:c.1660_1661del (p. D554Qfs*3)杂合变异,该变异被评估为致病性变异和遗传自母亲的变异。迄今为止,这两个变异还未见报道:结论:我们的研究发现了两个新的 TCOF1 基因致病变异,明确了特雷撤-科林斯综合征的病因。我们还丰富了特雷撤-科林斯综合征在中国人群中的表型谱和 TCOF1 基因变异谱,为临床诊断、治疗和遗传咨询提供了依据。
Two novel pathogenic variants in the TCOF1 found in two Chinese cases of Treacher Collins syndrome.
Background: Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology.
Methods: The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing.
Results: Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before.
Conclusion: Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.
期刊介绍:
Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care.
Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.