The Treacher Collins syndrome (TCOF1) gene product is involved in pre-rRNA methylation.
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Treacher Collins syndrome (TCS) is characterized by defects in craniofacial development, which results from mutations in the TCOF1 gene. TCOF1 encodes the nucleolar phosphoprotein treacle, which interacts with upstream binding factor (UBF) and affects transcription of the ribosomal DNA gene. The present study shows participation of treacle in the 2'-O-methylation of pre-rRNA. Antisense-mediated down-regulation of treacle expression in Xenopus laevis oocytes reduced 2'-O-methylation of pre-rRNA. Analysis of RNA isolated from wild-type and Tcof1+/- heterozygous mice embryos from strains that exhibit a lethal phenotype showed significant reduction in 2'-O-methylation at nucleotide C463 of 18S rRNA. The level of pseudouridylation of U1642 of 18S rRNA from the same RNA samples was not affected suggesting specificity. There is no significant difference in rRNA methylation between wild-type and heterozygous embryos of DBA x BALB/c mice, which have no obvious craniofacial phenotype. The function of treacle in pre-rRNA methylation is most likely mediated by its direct physical interaction with NOP56, a component of the ribonucleoprotein methylation complex. Although treacle co-localizes with UBF throughout mitosis, it co-localizes with NOP56 and fibrillarin, a putative methyl transferase, only during telophase when rDNA gene transcription and pre-rRNA methylation are known to commence. These observations suggest that treacle might link RNA polymerase I-catalyzed transcription and post-transcriptional modification of pre-rRNA. We hypothesize that haploinsufficiency of treacle in TCS patients results in inhibition of production of properly modified mature rRNA in addition to inhibition of rDNA gene transcription, which consequently affects proliferation and proper differentiation of specific embryonic cells during development. (+info)
Treacher Collins Syndrome with choanal atresia: a case report and review of disease features.
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Treacher Collins Syndrome--or mandibulofacial dysostosis--is a rare condition that presents several craniofacial deformities of different levels. This is a congenital malformation involving the first and second branchial arches. Incidence is estimated to range between 1-40,000 to 1-70,000 of live births. The disorder is characterized by abnormalities of the auricular pinna, hypoplasia of facial bones, antimongoloid slanting palpebral fissures with coloboma of the lower eyelids and cleft palate. Treacher Collins Syndrome is rarely associated with choanal atresia. A multidisciplinary team, including craniofacial surgeon, ophthalmologist, speech therapist, dental surgeon and otorhinolaryngologist, is the most appropriate setting to manage these patients. This study reports a rare case of Treacher Collins Syndrome with choanal atresia, presenting literature review and multidisciplinary intervention. (+info)
Association of Treacher Collins syndrome and translocation 6p21.31/16p13.11: exclusion of the locus from these candidate regions.
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Treacher Collins syndrome (TCS) is an autosomal dominant defect of craniofacial development which has not been chromosomally localized. We have identified a mother and two children who have TCS and also a balanced translocation t(6;16)(p21.31;p13.11), which suggested the possibility that the TCS locus might be located at one of the translocation breakpoints. These were defined by in-situ hybridization as 6p21.31 (by using loci in the HLA complex defined by the probes p45.1DP beta 003/HLA-DPB2 and pRS5.10/HLA class I chain) and 16p13.11 (by using probes pACHF1.3.2/D16S8 and VK45/D16S131). Pairwise and multipoint linkage analysis using localized chromosome 6 probes and chromosome 16 probes in 12 unrelated TCS families with multiple affected siblings excluded the TCS locus from proximity to both translocation breakpoints. These data were confirmed when a third affected child, who did not exhibit the translocation, was born to the mother. (+info)
The gene for Treacher Collins syndrome maps to the long arm of chromosome 5.
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Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. We have studied 12 unrelated TCS families with multiple affected individuals for linkage to five chromosome 5 markers. There is strong evidence demonstrating linkage to three of these markers. Multipoint linkage analysis places the mutation causing TCS in the interval between the gene for the glucocorticoid receptor and the anonymous marker D5S22, with a maximum multipoint lod score of 9.1. (+info)
Postaxial acrofacial dysostosis (Miller) syndrome: a new case.
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We describe a new case of postaxial acrofacial dysostosis (Miller) syndrome. This syndrome consists of mandibulofacial dysostosis, similar to that seen in Treacher Collins syndrome, and postaxial limb deficiency. The mode of inheritance remains uncertain. (+info)
Evaluation of craniofacial surgery in the treatment of facial deformities.
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Surgical access to the cranial, orbital, and facial areas, as developed by Tessier, has produced not only definitive repair of previously uncorrectable congenital deformities such as orbital hypertelorism and facial stenosis (e.g., Crouzon's, Apert's syndromes) but also has improved markedly the treatment of traumatic and neoplastic defects. The surgical approach allows complete dissection of facial soft tisses including the orbits from the underlying bones followed by corrective osteotomies and fixation. Mobilization of the frontal lobes through a frontal bone flap exposure may be required. The ramifications of this latest intrusion by surgeons into a previously inviolate anatomic area have involved neurosurgeons, ophthalmologists, anesthesiologists, and dental and psycho-social disciplines. The disciplines of genetics and embryology are being influenced by this new field of surgery, much as the study of immunology was influenced by transplantation surgery two decades ago. This report analyzes a 10 year experience with over 100 patients with emphasis on patient selection by disease, age, intellectual status, morbidity, complications, and the psycho-social reactions of patient and family. Procedures initially planned to correct dental and aesthetic defects are proving beneficial for other functions including hearing, taste and smell, articulation and tongue movement, respiratory function, vision, and possibly bone growth. The development of self image, a normal process always in operation, is also strikingly altered. These operations may last as long as 14 to 16 hours. We have had no deaths or postoperative blindness. One postoperative cerebrospinal fluid leak was successfully repaired. Three partial losses of bone grafts and four instances of late cellulitis have occurred. Prevention of infection seems related to avoidance of dead spaces and primary closure of all mucosal, dural, conjunctival and skin surfaces. (+info)
Prosthetic management of a patient with Treacher Collins syndrome.
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Treacher Collins syndrome encompasses a group of closely related defects of the head and neck. It is a rare syndrome characterized by bilaterally symmetrical abnormalities derived from the first and second brachial arches and the nasal placode. It is an autosomal dominant disorder and its occurence ranges from 1 in 25,000 to 1 in 50,000 live births. The facial appearance of these patients can be improved by either surgical or prosthetic rehabilitation. In this case report we are presenting the features of a 13-year-old boy with Treacher Collins syndrome. A multidisplinary approach was followed in managing the situation. The various treatment options and the steps involved in making an auricular prosthesis are also discussed. (+info)
Dental and facial bone abnormalities in pyknodysostosis: CT findings.
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Pyknodysostosis is an autosomal-recessive disorder of osteoclast dysfunction causing osteosclerosis, with associated maxillofacial anomalies. Multidetector CT with multiplanar and 3D reconstruction illustrated the pathologic findings in this case. Abnormalities included multiple retained deciduous teeth, unerupted teeth with associated follicles, an irregularly expanded alveolus and body of the mandible, and an obtuse mandibular angle. Volume-rendered imaging better delineated the irregular dentition, with crowding and retention of deciduous teeth. (+info)