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

Beygo, Jasmin; Buiting, Karin; Seland, Saskia; Lüdecke, Hermann Josef; Hehr, Ute; Lich, Christina; Prager, Bettina; Lohmann, Dietmar; Wieczorek, Dagmar

doi:10.1159/000335545

Cited by 21 publications

(17 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7 Heterozygous intragenic deletions in TCOF1 have been recently described as a rare cause of TCS. 8,9 To date, no correlations have been established between phenotypic variability and the location of the mutations within TCOF1. 2,10 Mutations and intragenic deletions in the POLR1D and POLR1C genes have been observed in a small subset of patients with TCS.…”

Section: Original Research Article Introductionmentioning

confidence: 99%

Treacher Collins syndrome: a clinical and molecular study based on a large series of patients

Vincent

Geneviève

Ostertag

et al. 2016

Genetics in Medicine

121

120

View full text Add to dashboard Cite

Purpose: Treacher Collins/Franceschetti syndrome (TCS; OMIM 154500) is a disorder of craniofacial development belonging to the heterogeneous group of mandibulofacial dysostoses. TCS is classically characterized by bilateral mandibular and malar hypoplasia, downward-slanting palpebral fissures, and microtia. To date, three genes have been identified in TCS:,TCOF1, POLR1D, and POLR1C. Methods:We report a clinical and extensive molecular study, including TCOF1, POLR1D, POLR1C, and EFTUD2 genes, in a series of 146 patients with TCS. Phenotype-genotype correlations were investigated for 19 clinical features, between TCOF1 and POLR1D, and the type of mutation or its localization in the TCOF1 gene. Results:We identified 92/146 patients (63%) with a molecular anomaly within TCOF1, 9/146 (6%) within POLR1D, and none within POLR1C. Among the atypical negative patients (with intellectual disability and/or microcephaly), we identified four patients carrying a mutation in EFTUD2 and two patients with 5q32 deletion encompassing TCOF1 and CAMK2A in particular. Congenital cardiac defects occurred more frequently among patients with TCOF1 mutation (7/92, 8%) than reported in the literature. Conclusion:Even though TCOF1 and POLR1D were associated with extreme clinical variability, we found no phenotype-genotype correlation. In cases with a typical phenotype of TCS, 6/146 (4%) remained with an unidentified molecular defect.

show abstract

Section: Original Research Article Introductionmentioning

confidence: 99%

Treacher Collins syndrome: a clinical and molecular study based on a large series of patients

Vincent

Geneviève

Ostertag

et al. 2016

Genetics in Medicine

121

120

View full text Add to dashboard Cite

show abstract

“…However, two alternatively spliced exons, exon 6A and exon 16A, may also be present in the minor transcripts . Several hundred largely family‐specific deletions, insertions, splicing, and nonsense mutations have subsequently been identified with partial gene deletions accounting for a small proportion of all mutations . The typical effect of the mutations is the introduction of a premature termination codon and the induction of nonsense‐mediated mRNA degradation, leading to haploinsufficiency of TCOF1 .…”

Section: Treacher Collins Syndromementioning

confidence: 99%

Rare syndromes of the head and face: mandibulofacial and acrofacial dysostoses

Terrazas

Dixon

Trainor

et al. 2017

WIREs Developmental Biology

View full text Add to dashboard Cite

Craniofacial anomalies account for approximately one-third of all congenital birth defects reflecting the complexity of head and facial development. Craniofacial development is dependent upon a multipotent, migratory population of neural crest cells, which generate most of the bone and cartilage of the head and face. In this review, we discuss advances in our understanding of the pathogenesis of a specific array of craniofacial anomalies, termed facial dysostoses, which can be subdivided into mandibulofacial dysostosis, which present with craniofacial defects only, and acrofacial dysostosis, which encompasses both craniofacial and limb anomalies. In particular, we focus on Treacher Collins syndrome (TCS), Acrofacial Dysostosis-Cincinnati Type as well as Nager and Miller syndromes, and animal models that provide new insights into the molecular and cellular basis of these congenital syndromes. We emphasize the etiologic and pathogenic similarities between these birth defects, specifically their unique deficiencies in global processes including ribosome biogenesis, DNA damage repair, and pre-mRNA splicing, all of which affect neural crest cell development and result in similar tissue-specific defects.

show abstract

“…Very recently, partial TCOF1 gene deletions have been identified as being causative of TCS in a subset of patients .…”

Section: Mandibulofacial Dysostosesmentioning

confidence: 99%

“…Very recently, partial TCOF1 gene deletions have been identified as being causative of TCS in a subset of patients (6,7). In 2011, two further genes, POLR1D and POLR1C , were reported to be the causative of TCS2 and TCS3, respectively (2).…”

Section: Treacher Collins Syndrome (Mim 154500)mentioning

confidence: 99%

Human facial dysostoses

Wieczorek

2013

Clinical Genetics

View full text Add to dashboard Cite

The human facial dysostoses can be subdivided into mandibulofacial dysostoses (MFDs) and acrofacial dysostoses (AFDs). The craniofacial phenotypes of the two groups of patients are similar. Both types are thought to be related to abnormal migration of neural crest cells to the pharyngeal arches and the face. The craniofacial anomalies shared by the two groups consist of downslanting palpebral fissures, coloboma of the lower eyelid, from which the eyelashes medial to the defect may be absent, hypoplasia of the zygomatic complex, micrognathia, and microtia, which is often associated with hearing loss. These facial deformities are associated with limb anomalies in the AFDs. All MFDs present with the typical craniofacial phenotype, but some have additional features that help to distinguish them clinically: intellectual disability, microcephaly, chest deformity, ptosis, cleft lip/palate, macroblepharon, or blepharophimosis. The limb anomalies in the AFDs can be classified into pre-axial, post-axial, and others not fitting into the first two AFD types. Of the pre-axial types, Nager syndrome and of the post-axial types, Miller syndrome are the best-known disorders of their AFD subgroups. Several other AFDs with unknown molecular genetic bases, including lethal ones, have been described. This article reviews the MFDs and AFDs published to date.

show abstract

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

Cited by 21 publications

References 56 publications

Treacher Collins syndrome: a clinical and molecular study based on a large series of patients

Treacher Collins syndrome: a clinical and molecular study based on a large series of patients

Rare syndromes of the head and face: mandibulofacial and acrofacial dysostoses

Human facial dysostoses

Contact Info

Product

Resources

About