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Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
背景：TreacherCollinsI综合征（TCS1，OMIM：154500）是一种常染色体显性疾病，具有一系列临床表现，例如颅面发育不良，包括眼睛和耳朵异常，小颌畸形，唇裂,以及反复呼吸道感染和传导性听力损失。本文报道2例TCOF1(OMIM:606847)基因变异的TreacherCollins综合征,具有临床特征，基因变异和病因。
方法：回顾性分析2例TCOF1基因变异导致的TreacherCollins综合征患者的临床资料。全外显子组测序(WES)检测患者TCOF1基因的致病变异,变异的验证通过Sanger测序进行确认。
结果：Proband1表现为双侧颅面畸形，传导性听力损失和反复呼吸道感染。Proband2显示双侧颅面畸形伴left裂，在她的家庭中也有类似的表现.她出生后不久因呼吸困难和喂养困难而死亡。WES在两个先证者中鉴定出TCOF1基因的两个新的致病变体，每个都有一个变体。根据美国医学遗传学和基因组学学院的说法，杂合变异NM_001371623.1：c.877del（p。在Proband1中检测到TCOF1基因的Ala293Profs*34），将其评估为可能的致病性（LP）和从头变体。在Proband2中发现的另一种变体是NM_001135243.1：c.1660_1661del（p。D554Qfs*3)杂合变异，这被评估为致病性变异和从母亲遗传的变异。迄今为止,这两种变体以前没有报道过。
结论：我们的研究发现了TCOF1基因的两个新的致病变异，并阐明了TreacherCollins综合征的病因。我们还丰富了中国人群TreacherCollins综合征的表型谱和TCOF1基因变异谱,为临床诊断提供依据,治疗和遗传咨询。
方法：回顾性分析2例TCOF1基因变异导致的TreacherCollins综合征患者的临床资料。全外显子组测序(WES)检测患者TCOF1基因的致病变异,变异的验证通过Sanger测序进行确认。
结果：Proband1表现为双侧颅面畸形，传导性听力损失和反复呼吸道感染。Proband2显示双侧颅面畸形伴left裂，在她的家庭中也有类似的表现.她出生后不久因呼吸困难和喂养困难而死亡。WES在两个先证者中鉴定出TCOF1基因的两个新的致病变体，每个都有一个变体。根据美国医学遗传学和基因组学学院的说法，杂合变异NM_001371623.1：c.877del（p。在Proband1中检测到TCOF1基因的Ala293Profs*34），将其评估为可能的致病性（LP）和从头变体。在Proband2中发现的另一种变体是NM_001135243.1：c.1660_1661del（p。D554Qfs*3)杂合变异，这被评估为致病性变异和从母亲遗传的变异。迄今为止,这两种变体以前没有报道过。
结论：我们的研究发现了TCOF1基因的两个新的致病变异，并阐明了TreacherCollins综合征的病因。我们还丰富了中国人群TreacherCollins综合征的表型谱和TCOF1基因变异谱,为临床诊断提供依据,治疗和遗传咨询。
