<i>TCOF1</i>
            gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout  its coding region

Wise, Carol A.; Chiang, Lydia C.; Paznekas, William A.; Sharma, Mridula; Musy, Maurice M.; Ashley, Jennifer; Lovett, Michael; Jabs, Ethylin Wang

doi:10.1073/pnas.94.7.3110

Cited by 163 publications

(168 citation statements)

References 34 publications

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“…4 TCOF1 encodes a low complexity, serine/alanine-rich protein called treacle, which has unique N and C termini and a large central repeat domain containing motifs shared with nucleolar trafficking proteins. 5 Treacle is therefore thought to be a nucleolar phosphoprotein involved in ribosomal DNA gene transcription. 6 The C-terminal region of treacle is important for localisation to the nucleolus 7,8 and the N-terminal region contains a LIS1 homology motif that may contribute to the regulation of microtubule dynamics, either by mediating dimerisation, or else by binding cytoplasmic dynein heavy chain or microtubules directly.…”

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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Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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“…Treacle consists of three distinct domains, unique amino and carboxy termini and a characteristic central repeat domain. 24,25 The carboxy terminus of Treacle contains multiple nuclear localization signals, which have been shown to drive nuclear import of the protein. 26,27 Biochemical assays have determined that Treacle is highly phosphorylated and contains a series of repeat units that have been identified within individual exons containing a number of potential sites for casein kinase II phosphorylation and protein kinase C phosphorylation, suggesting that phosphorylation is important for the correct function of the protein.…”

Section: Genetic and Biochemical Basis Of Tcsmentioning

confidence: 99%

Treacher Collins syndrome: etiology, pathogenesis and prevention

2008

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In association withTreacher Collins syndrome: etiology, pathogenesis and prevention Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development that arises as the result of mutations in the TCOF1 gene, which encodes a nucleolar phosphoprotein known as Treacle. Individuals diagnosed with TCS frequently undergo multiple reconstructive surgeries, which are rarely fully corrective. Identifying potential avenues for rescue and/or repair of TCS depends on a profound appreciation of the etiology and pathogenesis of the syndrome. Recent research using animal models has not only determined the cellular basis of TCS but also, more importantly, unveiled a successful avenue for therapeutic intervention and prevention of the craniofacial anomalies observed in TCS.

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“…4,10,11 The SNPs lying in the same or in adjacent exons to the one harboring the pathogenic mutations were ascertained to determine whether they were informative for determining the parental origin of the pathogenic mutation for each family. Intronic segments were screened through SSCP to detect novel SNPs.…”

Section: Selection Of Informative Markersmentioning

confidence: 99%

Parental origin of mutations in sporadic cases of Treacher Collins syndrome

et al. 2003

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In some autosomal dominant conditions, there is a correlation between new mutations and paternal age, with new mutations arising almost exclusively in the male germ line. To test this hypothesis in Treacher Collins syndrome, we analyzed 22 sporadic cases, determining the parental origin of the pathogenic mutation in 10 informative families. Mutations were found to be of both paternal and maternal origin, without a detectable parental age effect, confirming that a paternal age effect is not universal to all autosomal dominant disorders. A discussion on the parental origin of mutations and paternal age effect in other diseases is included.

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TCOF1 gene encodes a putative nucleolar phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding region

Cited by 163 publications

References 34 publications

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

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

Treacher Collins syndrome: etiology, pathogenesis and prevention

Parental origin of mutations in sporadic cases of Treacher Collins syndrome

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