Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome

Colla, The Treacher Collins Syndrome; Dixon, Jill; Edwards, Sara J.; Gladwin, Amanda J.; Dixon, Michael J.; Loftus, Stacie K.; Bonner, Cynthia A.; Koprivnikar, Kathryn; Wasmuth, John J.

doi:10.1038/ng0296-130

Cited by 337 publications

(55 citation statements)

References 35 publications

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“…A recent study showed that ubiquitin signaling can modify a ribosome biogenesis factor, TCOF1, during human neural crest differentiation (Figure 1b) [74••]. The role of TCOF1 in ribosome biogenesis has been extensively studied and mutations in Tcof1 cause Treacher Collins syndrome, a craniofacial disorder characterized by loss of cranial neural crest cells [75,76]. Tcof1 knockdown or Tcof1 haploinsufficiency in mice results in pre-rRNA synthesis defects [77].…”

Section: Ubiquitin Comes In Various Sizes and Shapes At The Ribosomementioning

confidence: 99%

An emerging role for the ribosome as a nexus for post-translational modifications

Şimşek

Barna

2017

Current Opinion in Cell Biology

111

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The ribosome is one of life’s most ancient molecular machines that has historically been viewed as a backstage participant in gene regulation, translating the genetic code across all kingdoms of life in a rote-like fashion. However, recent studies suggest that intrinsic components of the ribosome can be regulated and diversified as a means to intricately control the expression of the cellular proteome. In this review, we discuss advances in the characterization of ribosome post-translational modifications (PTMs) from past to present. We specifically focus on emerging examples of ribosome phosphorylation and ubiquitylation, which are beginning to showcase that PTMs of the ribosome are versatile, may have functional consequences for translational control, and are intimately linked to human disease. We further highlight the key questions that remain to be addressed to gain a more complete picture of the array of ribosome PTMs and the upstream enzymes that control them, which may endow ribosomes with greater regulatory potential in gene regulation and control of cellular homeostasis.

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Section: Ubiquitin Comes In Various Sizes and Shapes At The Ribosomementioning

confidence: 99%

An emerging role for the ribosome as a nexus for post-translational modifications

Şimşek

Barna

2017

Current Opinion in Cell Biology

111

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“…Treacher Collins syndrome occurs with an incidence of about 1 in 50,000 live births and is primarily associated with autosomal dominant mutations in the TCOF1 gene, which is located on chromosome 5 [40]. To date, over 200 largely family-specific mutations have been documented throughout the TCOF1 gene and these include deletions, insertions, splice site, missense and nonsense mutations (http://genoma.ib.usp.br/TCOF1_database/).…”

Section: Introductionmentioning

confidence: 99%

Ribosome biogenesis in skeletal development and the pathogenesis of skeletal disorders

Trainor

Merrill

2014

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

100

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The skeleton affords a framework and structural support for vertebrates, while also facilitating movement, protecting vital organs, and providing a reservoir of minerals and cells for immune system and vascular homeostasis. The mechanical and biological functions of the skeleton are inextricably linked to the size and shape of individual bones, the diversity of which is dependent in part upon differential growth and proliferation. Perturbation of bone development, growth and proliferation, can result in congenital skeletal anomalies, which affect approximately 1 in 3000 live births [1]. Ribosome biogenesis is integral to all cell growth and proliferation through its roles in translating mRNAs and building proteins. Disruption of any steps in the process of ribosome biogenesis can lead to congenital disorders termed ribosomopathies. In this review, we discuss the role of ribosome biogenesis in skeletal development and in the pathogenesis of congenital skeletal anomalies.

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“…2 Deleterious mutations in TCOF1 (OMIM *606847) are associated with TCS type 1 (OMIM #154500). 3 The longest transcript of TCOF1 comprises 26 exons, which include the alternatively spliced exons 6A and 19. 4 Other minor splice isoforms include transcripts lacking exon 6A, transcripts lacking exon 19 and transcripts that include a novel exon 16A.…”

Section: Introductionmentioning

confidence: 99%

Gross deletions in TCOF1 are a cause of Treacher–Collins–Franceschetti syndrome

et al. 2012

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Treacher-Collins-Franceschetti syndrome (TCS) is an autosomal dominant craniofacial disorder characterised by midface hypoplasia, micrognathia, downslanting palpebral fissures, eyelid colobomata, and ear deformities that often lead to conductive deafness. A total of 182 patients with signs consistent with a diagnosis of TCS were screened by DNA sequence and dosage analysis of the TCOF1 gene. In all, 92 cases were found to have a pathogenic mutation by sequencing and 5 to have a partial gene deletion. A further case had a novel in-frame deletion in the alternatively spliced exon 6A of uncertain pathogenicity. The majority of the pathogenic sequence changes were found to predict premature protein termination, however, four novel missense changes in the LIS1 homology motif at the 5¢ end of the gene were identified. The partial gene deletions of different sizes represent B5.2% of all the pathogenic TCOF1 mutations identified, indicating that gene rearrangements account for a significant proportion of TCS cases. This is the first report of gene rearrangements resulting in TCS. These findings expand the TCOF1 mutation spectrum indicating that dosage analysis should be performed together with sequence analysis, a strategy that is predicted to have a sensitivity of 71% for patients in whom TCS is strongly suspected.

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Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome

Cited by 337 publications

References 35 publications

An emerging role for the ribosome as a nexus for post-translational modifications

An emerging role for the ribosome as a nexus for post-translational modifications

Ribosome biogenesis in skeletal development and the pathogenesis of skeletal disorders

Gross deletions in TCOF1 are a cause of Treacher–Collins–Franceschetti syndrome

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