TCOF1 mutation database: Novel mutation in the alternatively spliced exon 6A and update in mutation nomenclature

Splendore, Alessandra; Fanganiello, Roberto Dalto; Masotti, Cibele; Morganti, Lucas S.C.; Passos‐Bueno, Maria Rita

doi:10.1002/humu.20159

Cited by 37 publications

(42 citation statements)

References 29 publications

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“…Mutation Surveyor software (SoftGenetics, State College, Philadelphia, PA, USA) was used to identify sequence variants, and in silico splice prediction software used to predict alterations to splice sites (Alamut version 1.5 or 2.0, Interactive Biosoftware, Rouen, France). Nomenclature for sequence variants is in accordance with HGVS guidelines (www.hgvs.org) using GenBank NCBI reference sequence NM_001135243.1 (this includes exon 6A, but excludes exon 16A), as recommended by Splendore et al 14 …”

Section: Pcr and Sequencingmentioning

confidence: 99%

“…The literature suggests that 62-82% of patients diagnosed with TCS have the diagnosis confirmed by sequence analysis of TCOF1, POLR1D or POLR1C, 1,2,12,13 however, the aetiology of the remainder remains uncertain. Gross deletions or other rearrangements of TCOF1 cannot be ruled out as they have only been investigated in one study by Splendore et al, 14 who found no alterations in seven patients. This study looks at a larger cohort of 182 subjects using sequencing and MLPA.…”

Section: Introductionmentioning

confidence: 99%

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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: Pcr and Sequencingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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“…The mutation was named according to the genomic reference (NT_029289) and the cDNA that corresponds to the major treacle isoform (NM_001135243.1) [6]. Mutation nomenclature is based on Human Genome Variation Society (H.G.V.S.)…”

Section: Introductionmentioning

confidence: 99%

Study of a Family Presenting Novel Mutation of the TCOF1 Gene Associated with Treacher Collins Syndrome

Dell'Edera¹

2012

J Genet Syndr Gene Ther

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“…A reduction of the number of these cells at a critical time point early in embryogenesis leads to the cranial malformations typical for TCS [Dixon et al, 2007;Trainor, 2010]. In humans the phenotype shows a high inter-and intrafamilial variability ranging from mild, sometimes unaffected mutation carriers to severe forms leading to intrauterine death Splendore et al, 2002;Dixon et al, 2004;Teber et al, 2004;Masotti et al, 2005]. The spectrum of mutations within the TCOF1 gene that causes TCS is very heterogeneous The Treacher Collins Syndrome Collaborative et al, 1996;Splendore et al, 2002Splendore et al, , 2005So et al, 2004;Teber et al, 2004;Horiuchi et al, 2005;Dixon et al, 2007;Masotti et al, 2009].…”

mentioning

confidence: 99%

“…Lich /Prager /Lohmann /Wieczorek Mol Syndromol 2011;2:53-59 54 no causative mutation has been found so far [Splendore et al, 2000;Teber et al, 2004;Horiuchi et al, 2005;Masotti et al, 2005].…”

mentioning

confidence: 99%

First Report of a Single Exon Deletion in TCOF1 Causing Treacher Collins Syndrome

et al. 2011

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Treacher Collins syndrome (TCS) is a rare craniofacial disorder characterized by facial anomalies and ear defects. TCS is caused by mutations in the TCOF1 gene and follows autosomal dominant inheritance. Recently, mutations in the POLR1D and POLR1C genes have also been identified to cause TCS. However, in a subset of patients no causative mutation could be found yet. Inter- and intrafamilial phenotypic variability is high as is the variety of mainly family-specific mutations identified throughout TCOF1. No obvious correlation between pheno- and genotype could be observed. The majority of described point mutations, small insertions and deletions comprising only a few nucleotides within TCOF1 lead to a premature termination codon. We investigated a cohort of 112 patients with a tentative clinical diagnosis of TCS by multiplex ligation-dependent probe amplification (MLPA) to search for larger deletions not detectable with other methods used. All patients were selected after negative screening for mutations in TCOF1, POLR1D and POLR1C. In 1 patient with an unequivocal clinical diagnosis of TCS, we identified a 3.367 kb deletion. This deletion abolishes exon 3 and is the first described single exon deletion within TCOF1. On RNA level we observed loss of this exon which supposedly leads to haploinsufficiency of TREACLE, the nucleolar phosphoprotein encoded by TCOF1.

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TCOF1 mutation database: Novel mutation in the alternatively spliced exon 6A and update in mutation nomenclature

Cited by 37 publications

References 29 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

Study of a Family Presenting Novel Mutation of the TCOF1 Gene Associated with Treacher Collins Syndrome

First Report of a Single Exon Deletion in TCOF1 Causing Treacher Collins Syndrome

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