TCOF1 pathogenic variants identified by Whole-exome sequencing in Chinese Treacher Collins syndrome families and hearing rehabilitation effect

Fan, Xinmiao; Wang, Yibei; Fan, Yue; Du, Huiqian; Luo, Nana; Zhang, Shuyang; Chen, Xiaowei

doi:10.1186/s13023-019-1136-z

Cited by 15 publications

(32 citation statements)

References 27 publications

(40 reference statements)

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“…Treacher Collins syndrome was first defined by the English ophthalmologist Edward Treacher Collins. During the early fetal development (5th‐8th weeks), the abnormal formation of the first and second branchial arches causes TCS, which results in profound craniofacial malformation 16 . TCS has typical bilateral facial features, such as hypoplasia of the facial bones, coloboma of the lid, downward slanting palpebral fissures, and a prominent nose.…”

Section: Discussionmentioning

confidence: 99%

“…Treacher Collins syndrome presents with complex mandibulofacial dysplasia and requires lifelong multidisciplinary interventions 16 . TCS phenotypes are extremely diverse, and the needs of TCS patients for aesthetic, functional, and the psychosocial interventions also vary.…”

Section: Discussionmentioning

confidence: 99%

“…However, the development of individualized treatment options is needed 17‐20 . Fan et al 16 reported that bone conduction hearing rehabilitation was a very helpful improvement measure for TCS patients with bilateral conductive hearing loss. In our study, proband 7 chose interventional surgery to improve hearing loss and correct facial deformity and had a good outcome.…”

Section: Discussionmentioning

confidence: 99%

“…According to the ACMG/AMP guidelines and InterVar software, six of the above variants were categorized as "pathogenic" and one was categorized as "likely pathogenic" ( Treacher Collins syndrome presents with complex mandibulofacial dysplasia and requires lifelong multidisciplinary interventions. 16 TCS phenotypes are extremely diverse, and the needs of TCS patients for aesthetic, functional, and the psychosocial interventions also vary. Some TCS patients choose general surgery to improve the presentation of mandibulofacial dysplasia.…”

Section: Discussionmentioning

confidence: 99%

“…However, the development of individualized treatment options is needed. [17][18][19][20] Fan et al 16 reported that bone conduction hearing rehabilitation was a very helpful improvement measure for TCS patients with bilateral con- In conclusion, we performed a mutation screening for seven TCS patients from seven unrelated families by using targeted NGS and Sanger sequencing. Currently, about 345 pathogenic/likely TA B L E 2 Classification of TCOF1 mutations in this study according to ACMG guideline pathogenic variants causing TCS are listed in HGMD.…”

Section: Discussionmentioning

confidence: 99%

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Mutation analysis of TCOF1 gene in Chinese Treacher Collins syndrome patients

Zhang

An²,

Xue

et al. 2020

Clinical Laboratory Analysis

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Background Treacher Collins syndrome (TCS) is a rare autosomal dominant or recessive disorder, that involves unique bilateral craniofacial malformations. The phenotypes of TCS are extremely diverse. Interventional surgery can improve hearing loss and facial deformity in TCS patients. Method We recruited seven TCS families. Variant screening in probands was performed by targeted next‐generation sequencing (NGS). The variants identified were confirmed by Sanger sequencing. The pathogenicity of all the mutations was evaluated using the guidelines of the American College of Medical Genetics and Genomics (ACMG) and InterVar software. Results Three frameshift variants, two nonsense variants, one missense variant, and one splicing variant of TCOF1 were identified in the seven TCS probands. Five variants including c.1393C > T, c.4111 + 5G>C, c.1142delC, c.2285_2286delCT, and c.1719delG had not been previously reported. Furthermore, we report the c.149A > G variant for the first time in a Chinese TCS patient. We provided prenatal diagnosis for family 4. Proband 7 chose interventional surgery. Conclusion We identified five novel variants in TCOF1 in Chinese patients with TCS, which expands the mutation spectrum of TCOF1 in TCS. Bone conduction hearing rehabilitation can improve hearing for TCS patients and prenatal diagnosis can provide fertility guidance for TCS families.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Mutation analysis of TCOF1 gene in Chinese Treacher Collins syndrome patients

Zhang

An²,

Xue

et al. 2020

Clinical Laboratory Analysis

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Identification of a novel gross deletion of TCOF1 in a Chinese prenatal case with Treacher Collins syndrome

Liu

Lin

Pang

et al. 2020

Molec Gen & Gen Med

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Background Treacher Collins syndrome (TCS) is the most common mandibulofacial dysostosis with an autosomal dominant or rarely recessive manner of inheritance. It is still challenging to make a definite diagnosis for affected fetuses with TCS only depending on the ultrasound screening. Genetic tests can contribute to the accurate diagnosis for those prenatal cases. Methods Targeted exome sequencing was performed in a fetus of a Chinese family, who presenting an abnormal facial appearance by prenatal 2D and 3D ultrasound screening, including micrognathia, nasal bridge pit, and abnormal auricle. The result was validated with multiplex ligation‐dependent probe amplification (MLPA) and real‐time quantitative PCR (qPCR). Results A novel 2–6 exons deletion of TCOF1 gene was identified and confirmed by the MLPA and qPCR in the fetus, which was inherited from the affected father with similar facial anomalies. Conclusion The heterozygous deletion of 2–6 exons in TCOF1 results in the TCS of this Chinese family. Our findings not only enlarge the spectrum of mutations in TCOF1 gene, but also highlight the values of combination of ultrasound and genetics tests in diagnosis of craniofacial malformation‐related diseases during perinatal period.

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Treacher Collins syndrome: Clinical report and retrospective analysis of Chinese patients

Pan

Chen

et al. 2020

Molec Gen & Gen Med

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Background Treacher Collins syndrome‐1 (TCS1; OMIM# 154500) is a rare autosomal dominant disease that is defined by congenital craniofacial dysplasia. Here, we report four sporadic and one familial case of TCS1 in Chinese patients with clinical features presenting as hypoplasia of the zygomatic complex and mandible, downslanting palpebral fissures, coloboma of the lower eyelids, and conductive hearing loss. Materials and Methods Audiological, radiological, and physical examinations were performed. Targeted next‐generation sequencing (NGS) was performed to examine the genetics of this disease in five probands, and Sanger sequencing was used to confirm the identified variants. A literature review discusses the pathogenesis, treatment, and prevention of TCS1. Results We identified a novel insertion of c.939_940insA (p.Gly314Argfs*35; NM_001135243.1), a novel deletion of c.1766delC (p.Pro589Leufs*7), two previously reported insertions of c.1999_2000insC (p.Arg667Profs*31) and c.4218_4219insG (p.Ser1407Valfs*23), and one previously reported deletion of c.4369_4373delAAGAA (p.Lys1457Glufs*12) in the TCOF1 gene. All five cases exhibited a degree of interfamilial and intrafamilial phenotypic variability. A review of the literature revealed no clear evidence of a genotype–phenotype correlation in TCS1. Conclusion Our results expand the variant spectrum of TCOF1 and highlight that NGS is essential for the diagnosis of TCS and that genetic counseling is beneficial for guiding prevention.

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TCOF1 pathogenic variants identified by Whole-exome sequencing in Chinese Treacher Collins syndrome families and hearing rehabilitation effect

Cited by 15 publications

References 27 publications

Mutation analysis of TCOF1 gene in Chinese Treacher Collins syndrome patients

Mutation analysis of TCOF1 gene in Chinese Treacher Collins syndrome patients

Identification of a novel gross deletion of TCOF1 in a Chinese prenatal case with Treacher Collins syndrome

Treacher Collins syndrome: Clinical report and retrospective analysis of Chinese patients

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