Mutation analysis of <i>TCOF1</i> gene in Chinese Treacher Collins syndrome patients

Zhang, Chuan; An, Li; Xue, Hong; Shen, Hao; Yan, Yousheng; Zhang, Qinghua; Jin, Xiaohua; Li, Qian; Zhou, Bingbo; Feng, Xuan; Ma, Panpan; Wang, Xing; Chen, Xue; Chen, Cuixia; Cao, Zanxia; Ma, Xu

doi:10.1002/jcla.23567

Cited by 9 publications

(15 citation statements)

References 18 publications

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“…The proband's parents had no abnormalities or hearing problems. Genetic analyses of the proband showed a previously reported variant c.4369_4373delAAGAA (p.Lys1457Glufs*12) in exon 24 of TCOF1 (Figure 3c), which may result in a premature stop codon causing translation of a truncated protein (Bowman et al, 2012; Chen et al, 2018; Conte et al, 2011; Li et al, 2019; Masotti et al, 2009; Splendore et al, 2000; Zhang et al, 2013, 2020). This variant was not identified by Sanger sequencing in either of his parents, confirmed a de novo status.…”

Section: Resultsmentioning

confidence: 93%

“…Two previously reported insertions of c.1999_2000insC (p.Arg667Profs*31; NM_001135243.1) and c.4218_4219insG (p.Ser1407Valfs*23) were detected in case 1 as well as case 2 and further confirmed by Sanger sequencing ( Bowman et al, 2012; Masotti et al, 2009). One previously reported de novo deletion of c.4369_4373delAAGAA (p.Lys1457Glufs*12) in the TCOF1 gene was identified in case 3 and this variant has been described as a hotspot variant that is frequently detected in TCS1 cases ( Bowman et al, 2012; Chen et al, 2018; Conte et al, 2011; Li et al, 2019; Masotti et al, 2009; Splendore et al, 2000; Zhang et al, 2013, 2020). A novel de novo insertion of c.939_940insA (p.Gly314Argfs*35) was detected in case 4.…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 93%

Section: Resultsmentioning

confidence: 99%

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

Pan

Chen

et al. 2020

Molec Gen & Gen Med

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“…Over 200 mutations have been reported in the TCOF1 gene including deletions, insertions, substitutions [ 15 , 22 , 23 , 24 , 25 , 26 , 27 ]. Exons 10, 15, 16, 23 and 24 are hotspots in TCOF1 .…”

Section: Geneticsmentioning

confidence: 99%

“…The longest insertion, c.484_668ins185bp, was localized to exon 5 in twin sisters [ 33 ]. Zhang et al [ 27 ] identified five novel variants (two nonsense, one missense and one splicing) in TCOF1 in Chinese patients. Zeng et al [ 26 ] reported a nonsense pathogenic variant (c.1622G > A) in exon 11 of TCOF1 .…”

Section: Geneticsmentioning

confidence: 99%

Treacher Collins Syndrome: Genetics, Clinical Features and Management

Marszałek-Kruk

Wójcicki

Dowgierd

et al. 2021

Genes

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Treacher Collins syndrome (TCS) is associated with abnormal differentiation of the first and second pharyngeal arches, occurring during fetal development. Features of TCS include microtia with conductive hearing loss, slanting palpebral fissures with possibly coloboma of the lateral part of lower eyelids, midface hypoplasia, micrognathia as well as sporadically cleft palate and choanal atresia or stenosis. TCS occurs in the general population at a frequency of 1 in 50,000 live births. Four subtypes of Treacher Collins syndrome exist. TCS can be caused by pathogenic variants in the TCOF1, POLR1D, POLR1C and POLR1B genes. Genetically, the TCOF1 gene contains 27 exons which encodes the Treacle protein. In TCOF1, over 200 pathogenic variants have been identified, of which most are deletions leading to a frame-shift, that result in the formation of a termination codon. In the presented article, we review the genetics and phenotype of TCS as well as the management and surgical procedures utilized for treatment.

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“…It remains elusive whether abnormal expression or deubiquitinase activity of CYLD can affect the length of primary nerve axons in mice 27 . A few studies have reported the molecular mechanisms by which different post‐translational modifications of proteins affect hearing 28,29 . However, there have been relatively few reports describing the role of CYLD in hearing and neurology.…”

Section: Introductionmentioning

confidence: 99%

CYLD deficiency causes auditory neuropathy due to reduced neurite outgrowth

Yang

et al. 2021

Clinical Laboratory Analysis

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Background Auditory neuropathy is a cause of hearing loss that has been studied in a number of animal models. Signal transmission from hair cells to spiral ganglion neurons plays an important role in normal hearing. CYLD is a microtubule‐binding protein, and deubiquitinase involved in the regulation of various cellular processes. In this study, we used Cyld knockout (KO) mice and nerve cell lines to examine whether CYLD is associated with auditory neuropathy. Methods Hearing of Cyld KO mice was studied using the TDT RZ6 auditory physiology workstation. The expression and localization of CYLD in mouse cochlea and cell lines were examined by RT‐PCR, immunoblotting, and immunofluorescence. CYLD expression was knocked down in SH‐SY5Y cells by shRNAs and in PC12 and N2A cells by siRNAs. Nerve growth factor and retinoic acid were used to induce neurite outgrowth, and the occurrence and length of neurites were statistically analyzed between knockdown and control groups. Results Cyld KO mice had mild hearing impairment. Moreover, CYLD was widely expressed in mouse cochlear tissues and different nerve cell lines. Knocking down CYLD significantly reduced the length and proportion of neurites growing from nerve cells. Conclusions The abnormal hearing of Cyld KO mice might be caused by a decrease in the length and number of neurites growing from auditory nerve cells in the cochlea, suggesting that CYLD is a key protein affecting hearing.

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Mutation analysis of TCOF1 gene in Chinese Treacher Collins syndrome patients

Cited by 9 publications

References 18 publications

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

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

Treacher Collins Syndrome: Genetics, Clinical Features and Management

CYLD deficiency causes auditory neuropathy due to reduced neurite outgrowth

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